Padabagian kepala virus diselubungi oleh kapsid, yaitu selubung protein yang tersusun oleh protein. Bentuk kapsid sangat bergantung pada jenis virusnya. Kapsid virus bisa berbentuk bulat, polihedral, heliks, atau bentuk lain yang lebih kompleks. Kapsid tersusun atas banyak kapsomer atau sub-unit protein. Kapsid adalah lapisan berupa rangkaian ï»żSpike berfungsi sebagai proses pelekatan virus pada sel inang Fungsi spike pada virus untuk pelekatan virus pada permukaan sel inang yang spesifik Proteinmerupakan senyawa utama penyusun capsid (ind: kapsid) yang membungkus asam nukleat pada tubuh virus. Kapsid yang tersusun dari protein ini bila terisi asam nukleat (DNA atau RNA) disebut dengan nukleokapsid (nucleocapsid) Lipid yang ada pada virus merupakan jenis fosfolipid, gikolipid, kolestrol dan beberapa lemak alami yang lain. Lemak merupakan komponen utama penyusun envelope (selubung). Senyawa-senyawa lain yang belum diketahui. Jenis-jenis virus | Photo by U.S. federal
spike pada virus tersusun atas protein dan karbohidrat yang disebut...1. spike pada virus tersusun atas protein dan karbohidrat yang disebut...2. spike pada virus tersusun atas protein dan karbohidrat yang disebut3. spike virus tersusun atas protein dan kharbohidrat yng disebut4. Susunan dinding sel jemur terdiri atas karbohidrat dan protein yang disebut5. kapsid virus tersusun atas subunit-subunit protein yang disebut6. virus tersusun atas selubung protein yang disebut ?7. Virus tersusun atas selubung protein yang disebut ...... 8. Virus tersusun atas selubung protein yang disebut..9. Virus tersusun atas selubung protein yang disebut ....... 10. virus tersusun atas selubung protein yang di sebut 11. virus tersusun atas selubung protein yang disebut ....12. sebutkan unsur penyusun karbohidrat, lemak, dan protein13. Virus tersusun atas lubang protein yg di sebut14. sebutkan 3 unsur protein yang sama dengan penyusun karbohidrat15. sebutkan unsur penyusun karbohidrat, lemak, dan protein16. selubung virus tersusun atas... a. protein b. asam inti c. lemak d. karbohidrat e. RNA17. Virus tersusun atas selubung protein yang disebut apakah?18. Kapsid virus tersusun atas subunit subunit protein yqng di sebut19. Selubung virus yang tersusun atas molekul protein disebut 20. Virus tersusun atas selubung protein yang disebut dengan uraian.... [tex] Sitologi, Virologi [/tex]Protein dan karbohidrat akan menyatu membentuk komponen lipopolisakarida. Lipopolisakarida ini dapat menyusun spike virus dibawah tabung virus. 2. spike pada virus tersusun atas protein dan karbohidrat yang disebut Spike pada virus tersusun atas protein dan karbohidrat yang disebut Kapsid 3. spike virus tersusun atas protein dan kharbohidrat yng disebut glikoprotein atau glikopeptidaJawaban Glikoprotein Glikopeptida . . . 4. Susunan dinding sel jemur terdiri atas karbohidrat dan protein yang disebut Kitin 5. kapsid virus tersusun atas subunit-subunit protein yang disebut RNAribo nukleat acid atau DNAdeoksiribo nukleat acid 6. virus tersusun atas selubung protein yang disebut ? selubung protein disebut kapsid 7. Virus tersusun atas selubung protein yang disebut ...... SoalVirus tersusun atas selubung protein yang disebut ......Jawaban dengan penjelasanKapsidVirus memiliki struktur tubuh yang sangat sederhana. Virus hanya memiliki satu macam materi genetik yang dikelilingi oleh suatu protein pelindung yang disebut kapsid. Sehingga, selubung protein pada virus dinamakan kapsid. Bukaanmaen 8. Virus tersusun atas selubung protein yang disebut.. kapsid gan bentukny juga beragamDNA atau RNA yang dikelilingi oleh suatu protein pelindung yang disebut kapsid. 9. Virus tersusun atas selubung protein yang disebut ....... Jawabankapsid atau capsidsPenjelasansemoga membantu 10. virus tersusun atas selubung protein yang di sebut selubung protein kapsidvirus hanya tersusun atas selubung kapsid selubung kapsid yang tersusun oleh molekul protein. 11. virus tersusun atas selubung protein yang disebut .... selubung protein disebut kapsitnama selubung protein penyusun virus adalah kapsid 12. sebutkan unsur penyusun karbohidrat, lemak, dan protein KarbohodratC. H. OLemakC. H. OProteinC. H. O. N. Kadang ada S. PC karbonH hidrigenO oksigenN nitrogenS sulphurP phospat 13. Virus tersusun atas lubang protein yg di sebut KapsidKamis 13-12-2018 14. sebutkan 3 unsur protein yang sama dengan penyusun karbohidrat 3 unsur tersebut yaitu karbon C, oksigen O serta hidrogen H 15. sebutkan unsur penyusun karbohidrat, lemak, dan protein -unsur penyusun karbohidrat adalah Karbon C, Hidrogen H dan Oksigen O.-unsur penyusun lemak adalah Karbon C, Hidrogen H dan Oksigen O.-unsur penyusun protein adalah Karbon C, Hidrogen H, Oksigen O, dan Nitrogen N. Terkadang protein juga mengandung unsur Posfor P dan Sulfur S 16. selubung virus tersusun atas... a. protein b. asam inti c. lemak d. karbohidrat e. RNA kalau memurutku jwbannya e. RNA 17. Virus tersusun atas selubung protein yang disebut apakah? virus terbungkus oleh selubung protein yang disebut kapsid 18. Kapsid virus tersusun atas subunit subunit protein yqng di sebut kapsomer....................Terbuat dari protein yang disebut protomerSemoga membantu ya 19. Selubung virus yang tersusun atas molekul protein disebut AnsSelubung pada virus yang tersusun atas molekul protein disebut selubung selubung sebagai pelindung genome virussemoga membantu. 20. Virus tersusun atas selubung protein yang disebut dengan uraian.... Virus tersusun atas selubung protein yang disebut dengan uraian membantu.
Dalambeberapa tahun terakhir, resistensi antibiotik muncul sebagai masalah kesehatan global yang perlu mendapatkan perhatian serius. Jenis antibiotik baru yang ditemukan semakin jarang, namun jumlah antibiotik yang berkurang efektivitasnya meningkat dari tahun ke tahun. Bakteri yang resisten terhad Integrated Methods in Protein Biochemistry Part AMax Meyrath, ... on behalf of the CON-VINCE Consortium, in Methods in Enzymology, 20222 Before you beginThis virus-free assay uses two cell lines expressing respectively the viral spike and host cell receptor ACE2 on their surface and builds on the principle that cell membranes merge upon spike-ACE2 interaction. Each cell line additionally expresses one part of the NanoLuc luciferase HiBiT or LgBiT that on their own do not emit light, but when brought together, quickly self-complement due to their high affinity for each other to reconstitute a fully functional NanoLuc HiBiT technology, Promega. When co-incubated, these two cell lines are able to form syncytia through their cell membrane fusion facilitated by the spike-ACE2 interaction, in turn allowing rapid and spontaneous complementation of the cytoplasmic NanoLuc fragments and giving rise to ultra-bright bioluminescence in the presence of a specific substrate Fig. 1. Similar to classical viral neutralization assays, pre-incubation with neutralizing antibodies blocking the spike-ACE2 interaction prevents syncytia formation, which can be titrated and quantified by measuring the reduced light emission in comparison to cells that were not treated with neutralizing antibodies Fig. 1A and C.Fig. 1. Cell fusion assay based on high-affinity NanoLuc complementation HiBiT A Schematic representation of the assay set-up. LgBiT and spike-expressing HEK293T cells are mixed with HiBiT- and ACE2-expressing Vero E6 cells and co-incubated overnight. Upon spike interaction with ACE2, cell membranes merge, forming a multinucleated syncytium and enabling complementation of both NanoLuc fragments, eventually leading to light emission upon substrate addition. Pre-incubation of spike-expressing cells with neutralizing antibodies will prevent the spike–ACE2 interaction and limit syncytia formation. Multiple sera can be tested simultaneously in 96- or 384-well format, enabling high-throughput screening of samples. B Representative microscopy pictures, illustrating syncytium formation between Vero E6 cells expressing an mKOrange-tagged membrane marker and HEK293T cells expressing a NeonGreen cytoplasmic marker. DAPI-stained nuclei are depicted in blue. C Representative picture of a 96-well plate after substrate addition taken with an ordinary mobile phone camera Huawei p20 Pro. The intense blue bioluminescent signal emitted by the NanoLuc is well visible even with the naked eye. No light is emitted from wells where cells did not efficiently form syncytia, indicative of the presence of neutralizing A Figure was created using the material, vectors and protocols described below, this “SARScytium” assay can easily and reproducibly be performed using transiently transfected cells, where one cell line is transfected with viral spike and LgBiT, whereas the other cell line is transfected with HiBiT and ACE2 Fig. 1A. The approach using transient transfections allows for high versatility and flexibility of the assay with easy and fast adaptability to spike variants. This can be of particular interest given that the antibody neutralization profile considerably varies between the different spike variants and the high probability of emergence of new variants Duarte et al., 2022; Harvey et al., 2021. Alternatively, cells stably expressing the required proteins can be used. This accounts especially for ACE2, where a variety of cells stably expressing ACE2 are commercially available, such as Vero E6 cells that endogenously express ACE2, or HEK or HeLa cells exogenously overexpressing ACE2 together or not with the protease TMPRSS2 that serves as a co-factor for SARS-CoV-2 infection and is implicated in spike priming on the full chapterURL coronavirus infections of the lower respiratory tract and their preventionN. Petrovsky, in The Microbiology of Respiratory System Infections, 20163 Recombinant spike protein vaccinesA major advance in vaccine development was the identification that the SARS virus spike S protein mediates cell entry via its ability to bind angiotensin-converting enzyme 2 and CD209L, thereby triggering virus endocytosis into target A human monoclonal antibody binding the S protein N-terminal domain was shown to be able to block infection, thereby identifying S protein as a major target of SARS virus neutralizing Consistent with this, monkeys could be protected against SARS infection by intranasal immunization with a S protein-encoding live parainfluenza S protein was also shown to be the target of CD4 and CD8 T cell responses suggesting these may also be important to SARS A recombinant S protein vaccine was manufactured using an insect cell expression system but was found to be considerably less immunogenic that inactivated whole virus vaccine, requiring ∌100 times more antigen to achieve the same level of Attempts to improve the immunogenicity of S protein vaccine by formulation with alum adjuvant again resulted in severe lung eosinophilic immunopathology in response to SARS virus infection, marking this as another potentially unsafe This confirmed that the problem of lung eosinophilic immunopathology was not just confined to inactivated or nucleocapsid protein vaccines but was a more general problem of vaccines made from any SARS virus full chapterURL VaccinesJaap W. Back, Johannes Langedijk, in Advances in Immunology, 20122 Stabilizing AntigensThe detailed structural knowledge on many neutralization sites, the location of some conserved exposed surfaces on the native viral spike, and the general architecture and dynamics of the labile structure reveals some clues of how to stabilize the spike in order to induce such broadly neutralizing way of using the structural knowledge for a recombinant protein-based vaccine is to engineer, modify, or stabilize the labile spike in such a way that the recombinant soluble protein mimics the prefusion native trimer that can cross-react with all the broadly neutralizing antibodies and remains stable in a vaccine adjuvant. Several approaches have been applied successfully to stabilize the case the immunogen is based on the soluble envelope protein, the deletion of the membrane anchor destabilizes the trimer which can be compensated by inclusion of heterologous trimerization domains Yang et al., 2000. Additionally, the prefusion conformation can be stabilized by preventing the FP from swinging out and the gp120 head to detach. A straightforward solution to fix the FP in its prefusion position and obstruct the refolding of gp41 into the stable postfusion conformation is to prevent the cleavage of the precursor gp160 into mature gp120–gp41 heterodimer Yang et al., 2000. Alternatively, to increase the chance of maintaining the FP in its native, probably buried, position, gp120 and gp41 can be covalently linked by the introduction of an intermolecular disulfide bridge Binley et al., 2000; Yang et al., 2000. Although it has been possible to engineer a disulfide with trial and error, high-resolution detail of the structure would permit rational introduction of stabilizing disulfide bonds that connect the heterodimer. Disulfide bridges have also been used for the intramolecular stabilization of the flexible regions within the subunits Dey et al., 2009; Zhou et al., 2007. Constructing a heat-stable foot-and-mouth disease vaccine by disulfide engineering came within reach when the crystal structure of the viral capsid was solved Mateo et al., 2008 and also the atomic-level resolution of the complete prefusion spike of HIV will undoubtedly contribute to structure-based design of inter- and intramolecular disulfides without going through the arduous path of trial and full chapterURL East Respiratory Syndrome-Coronavirus MERS-CoV InfectionJaffar A. Al-Tawfiq, Ziad A. Memish, in Emerging Infectious Diseases, 20144 Which Factors are Involved in Disease Pathogenesis? What are the Pathogenic Mechanisms?The pathogenesis of the disease has been elucidated in recent studies. MERS-CoV has spike glycoprotein S that targets the cellular receptor, dipeptidyl peptidase 4 DPP4.12,13 This viral spike has a putative receptor-binding domain RBD.13 MERS-CoV RBD has a core and a receptor-binding subdomain, which interacts with DPP4 ÎČ-propeller MERS-CoV MERS-CoV spike protein interacts with CD26 also known as DPP4 and causes viral attachment to host cells and virus-cell This is thought to be the first step in viral infection. The MERS-CoV infection results in profound apoptosis of infected respiratory cells within 24 full chapterURL Angel, ... Greenberg, in Encyclopedia of Virology Third Edition, 2008MorphologyRotaviruses were given their name because, when examined by classical electron microscopy, they appear as wheel rota-shaped, 70 nm particles. However, by cryoelectron microscopy a method that permits visualization of the viral spikes, the viral diameter is 100 nm Figure 1. Using this method, the virus particle has been shown to be formed by three concentric layers of proteins the core comprises viral structural protein 2 VP2, the RNA-dependent RNA polymerase VP1, guanyl tranferase VP3, and the viral genome Figure 1, the intermediate layer is formed by structural protein VP6, the most abundant and most antigenic viral protein, and the external layer comprises 780 copies of glycoprotein VP7 and 60 viral spikes formed by VP4. The surface of the virion has three types of pores that penetrate into the interior of the capsid. These channels seem to be important during viral replication, allowing exchange of compounds in aqueous solution to the inside of the capsid and the export of nascent RNA 1. An artist's reconstruction based on cryoelectron microscopy studies of an RV particle. Shown are the seven structural proteins, and the viral RNA. Reproduced with permission from Andrew Swift, Swift RV structural proteins and nonstructural proteins NSPs have been crystallized, permitting the initiation of detailed molecular studies of viral physiology. By this method, the viral spikes have been shown to consist of VP4 trimers, the structure of which rearranges upon trypsin cleavage a process that enhances viral infection and probably again on entry into the cell. These changes resemble the conformational transitions of membrane fusion proteins of enveloped viruses. The crystal structure of the viral hemaglutinin VP8 VP4 is cleaved by trypsin into VP8 and VP5 that contains several virus-neutralizing epitopes has also been determined. Details of the characteristics and function of the viral proteins are described elsewhere in this full chapterURL Angel, ... Greenberg, in Reference Module in Biomedical Sciences, 2014MorphologyRotaviruses were given their name because, when examined by classical electron microscopy, they appear as wheel rota-shaped, 70 nm particles. However, by cryoelectron microscopy a method that permits visualization of the viral spikes, the viral diameter is 100 nm, with an icosahedral structure T = 13 l Figure 1, and formed by three concentric layers of proteins. The core comprises three viral structural proteins VP and the 11 segments of dsRNA in the viral genome 120 copies of the scaffolding protein VP2, and anchored to each segment of dsRNA are the RNA-dependent RNA polymerase VP1 and the guanyl tranferase and methyltransferase VP3 Figure 1. The intermediate layer is made up of 260 trimers of the structural protein VP6, the most abundant and most antigenic viral protein. Particles with these protein layers are non-infectious but transcriptionally active and called double layered particles DLP. Their surface has 132 channels of three types that penetrate into the interior of the capsid. These channels are important during viral replication, allowing exchange of compounds in aqueous solution to the inside of the capsid and the export of nascent RNA transcripts. The external layer comprises 260 trimers of the glycoprotein VP7, which depend on bound calcium ions for stability, and 60 trimeric spikes formed by 1. An artist's reconstruction based on cryoelectron microscopy studies of an RV particle. Shown are the seven structural proteins, and the viral with permission from Andrew Swift, Swift RV structural proteins and nonstructural proteins NSPs have been crystallized, permitting detailed molecular studies of viral physiology. Using this method, the rearrangement of the viral spike protein VP4 upon trypsin cleavage a process that greatly enhances viral infection has been characterized The cleavage of VP4 by trypsin into VP8* and VP5*, which remain non-covalently associated with each other on the virion surface –VP5* being the proximal portion– generates a “rigidification” of the spike. These changes resemble the conformational transitions of membrane fusion proteins of enveloped viruses. Structure-based epitopes for neutralizing antibodies have been identified on the two RV outer layer proteins for VP7 two unique areas are targeted by neutralizing antibodies, some of which stabilize the capsid and prevent viral uncoating. The viral hemaglutinin VP8* contains at least four virus-neutralizing epitopes and antibodies directed against these epitopes probably block virus attachment. Antibodies directed at VP5* appear to neutralize the virus by inhibiting cell entry during capsid uncoating. Details of the characteristics and function of the viral proteins are described elsewhere in this full chapterURL Envelope Proteins of the BunyaviralesPablo Guardado-Calvo, FĂ©lix A. Rey, in Advances in Virus Research, 201710 Hantavirus Gn Is Homologous to Alphavirus E2Class II viral fusion proteins function together with an accompanying protein, which is released first from the same polyprotein precursor and can interact cotranslationally and in cis with the fusion protein, helping avoid premature activation in the secretory pathway. The evolution of both proteins is closely related because of structural and functional constraints. The glycoprotein complex in Alphaviruses is produced as an immature p62-E1 heterodimer, which trimerises to form the viral spikes. Furin maturation of immature p62 into mature E3-E2 proteins primes the viral spikes in the Golgi apparatus and renders E1 fusion competent. The structures of the immature p62-E1 heterodimer and mature E3–E2–E1 heterotrimers were described Voss et al., 2010, showing that E2 is folded in three distinct globular domains termed A, B, and C, organized around a central “ÎČ-ribbon” structure with characteristic “archs” Figs. 2D and 5B. The E1 TMIR is buried in between domains A and B of E2, and domain C contacts domain III of E1 near the viral membrane. Together with domain A, domain C is involved in threefold contacts stabilizing the trimeric 5. Comparison of the crystal structures of Puumala virus hGn A and Chikungunya virus E2 B. The structures are color-coded by domains domain A in blue, domain B in green, and domain C in cyan. The central domain is colored magenta for the region of the ÎČ-ribbon going from domain A to B, and yellow for the connection from domain B to C. C and D topology diagrams of domains A and B panels C and D, respectively. Chikungunya virus E2 domains are shown on the left and Hantavirus hGn on the right. Although there is an important insertion between strands at different locations between strands B and C in E2 and between C and D in hGn, the topological arrangement of the ÎČ-strands in the A domains in E2 and hGn is the same but the A strand in purple has switched ÎČ-sheets. In the case of domain B, the topology is identical. In hGn, domain A corresponds to residues 27–182, and domain B to residues 294–368. There is an insertion augmenting the region corresponding to the ÎČ-ribbon connector, which is represented in gray. The way the polypeptide chain exits domain A and enters the ÎČ-ribbon through an “arch” Voss et al., 2010 panels A and B is also conserved between E2 and hGn. The structure of hGn was obtained in the absence of hGc, and it is conceivable that domains A and B may have collapsed against each other without hGc. In the Chikungunya virus E2/E1 heterodimer, the domains are arranged around the rod-like E1, as represented in Fig. 2D. Only a structure of an hGn/hGc heterodimer can resolve this bunyaviruses, the mechanism to avoid premature fusion in the secretory pathway is not understood, and the lack of an internal cleavage site in Gn suggests that the maturation mechanism must be different to that reported for alphaviruses and flaviviruses. The structure of the N-terminal two-thirds of Gn from Puumala hantavirus hGn, the first structure of a bunyavirus Gn protein was recently determined using X-ray crystallography Li et al., 2016 and docked into a 16 Å resolution cryoelectron tomography cryo-ET map of Tula hantavirus, thereby providing the first partial glimpse of the hantavirus ultrastructural organization. The structure showed that hGn has two domains folded as a ÎČ-sandwich, which in spite of having insertions in different locations—which is the likely reason why current automated servers for structural comparisons do not detect the structural homology—exhibit the same topology of the corresponding domains termed A and B in alphavirus E2 Fig. 5. Moreover, the two ÎČ-sandwich domains are connected in a very similar way by a central ÎČ-ribbon structure with ÎČ-arches. Furthermore, secondary structure predictions for the absent C-terminal third domain of Gn suggest that it is also ÎČ-sheet-rich, with a size similar to that domain C of alphavirus E2 Fig. 5.In addition, the organization of the alphavirus and hantavirus spikes also shows similarities. The mature alphavirus particles are organized in an icosahedral capsid with triangulation number T = 4. They contain 80 trimeric spikes formed of E2 and E1 protomers. Docking the atomic model from the crystal structure of the E2/E1 heterodimer into cryo-EM reconstructions of alphavirus particles has shown that E2 forms homotrimers at the center of each spike, making all of the intraspike contacts, whereas E1 is peripheral and establishes quasi twofold homocontacts with E1 between adjacent spikes on the virion. The organization of the hantaviral particles is similar. The virions are pleomorphic in shape but are decorated by patches of spikes that form local high-order lattices with quasi fourfold symmetry. The cryo-ET reconstruction combined with docking the crystal structure of PUUV Gn into the segmented density has allowed to assign densities to Gn and Gc. The hantaviral spike is composed of two different regions, an elongated peripheral stalk that crosslinks diagonally different spikes and a central region located around the quasi fourfold axis of the tetrameric spikes. The model proposed suggests that Gn would be placed at the center of the spike, forming homotetramers, and accounting for most of the intraspike contacts and Gc would be placed peripherally, forming homodimers, and linking together adjacent spikes. This organization thus has important similarities with that of the alphaviruses, in spite of the differences between trimer vs tetramer full chapterURL Cellular and Molecular Biology of HIV-1 Broadly Neutralizing AntibodiesBarton F. Haynes, ... Gary J. Nabel, in Molecular Biology of B Cells Second Edition, 20152 Highly Conserved Structures on HIV-1 EnvHIV-1 Env is composed of three identical gp160 protomers. Surface gp160 precursor molecules are cleaved by cellular furin proteases, and the mature Env spike consists of a trimer of noncovalently associated gp120 and gp41 subunits Figure 1. HIV-1 Env mediates virus–cell fusion through three major steps. First, it engages host cell CD4, the primary HIV-1 receptor. This interaction results in an activated intermediate conformation that engages a secondary chemokine receptor, usually CCR5 and sometimes CXCR4. In the third step, the gp41 subunit rearranges into a six-helix bundle that causes hemifusion of the viral and cell surface membranes Figure 2 [41]. Antiviral neutralizing antibodies must bind either to the prefusion native viral spike or to an Env intermediate to block the virus–cell 1. Structure of the open conformation of trimeric envelope Env at subnanometer resolution.A Side view of the structure of trimeric Env bound to 17b Fab. The map was fitted with three copies of the X-ray structure for the gp120–17b portion of the 1GC1 coordinates with gp120 red and 17b Fv fragments light chain, yellow; heavy chain, green. One copy of the gp41 N-terminal helix cyan of 1AIK coordinates N34 was fitted individually into each of the three densities, which occupy the central region of the spike that is essentially a cavity in the unliganded state. B Side view of the density map from the unliganded native trimer, with the three gp41 N-terminal helices cyan superimposed to show that, in the open conformation, they occupy the solvent-filled cavity in the density map of the unliganded Ref. [41].FIGURE 2. Model for the mechanism of envelope Env CD4- or coreceptor-triggered activation of the Env spike forms an activated intermediate in which the N-terminal gp41 helices are vulnerable to neutralizing ligands. The prehairpin intermediate is formed upon insertion of the fusion peptide into the target cell membrane and dissociation of gp120, leading to the formation of the six-helix bundle state and subsequent fusion between viral and target cell Ref. [41].Numerous bnAbs have been isolated from individuals identified within cohorts with plasma neutralizing activity against diverse strains. BnAbs recognize one of at least four highly conserved yet vulnerable regions of Env the membrane proximal external region MPER of gp41 [18,20,42], a peptide-glycan epitope involving the V1V2 domain V1V2 glycan [16,22], a gp120 outer-domain glycan or peptide-glycan region V3 glycan [43,44], and the CD4 binding site CD4bs region of gp120 [19,23–25,45,46] Table 1. Recently, a fifth bnAb epitope composed of both the gp41 and gp120 subunits of Env has been defined [46a,46b,46c,46d]. Importantly, advances in cryoelectron microscopy and crystal structures have provided new insights into the native prefusion structure and the conformation of the HIV-1 Env spike [52–54]. Together with the detailed atomic level structures of bnAbs bound to their cognate epitopes, these Env trimeric structures provide tools that facilitate structure-based vaccine design [55–58].TABLE 1. Genetic Characteristics of HIV-1 Broadly Neutralizing Monoclonal AntibodiesViral EpitopeAntibody Binding CharacteristicsaAntibody Clonal FamilyIsotype and SubclassbHeavy Chain V-GeneLight Chain V-Gene Îș or λCDRH3 Length Kabat AAcVH Mutation nt%dVH Mutation AA%dNeutralization BreadtheNeutralization PotencyfPolyreactivegReferencesMPER of gp41Contiguous sequence2F5IgG32–5Îș1-13221415++++Yes[47]4E10IgG31–69Îș3-20181420++++++Yes[48] PG16NR3–33λ2-142812–1317–20++++++No[12]CH01–04IgG13–20Îș3-202414–1723–29+++Noh[16]PGT 141–145NR1–8Îș2-2831–3212–1821–29++++++NR[43]Outer domain glycanGlycan only2G12IgG13–21Îș1-5142132+++NR[44]V3-glycanPeptidoglycanPGT121–123NR4–59λ3-212417–2121–27++++++NR[43]PGT125–131NR4–39λ2-81915–2323–33++++++NR[43]PGT135–137NR4–39Îș3-151817–2025–29+++NR[43]CD4 binding siteCDRH3 loopb12NR1–3Îș3-20181320+++Noi[50]No liganded structureHJ16NR3–30Îș4-1191537+++NR[45]CDRH3 loopCH103–106IgG14–59λ3-11314–1622++++Yesj[19]Mimics CD4 via CDRH2VRC01–03IgG11–2Îș3-20m12–1430–3240–48+++++++No[23,51]VRC-PG04, 04bIgG11–2Îș3-20143038–39++++++No[24]VRC-CH30–34IgG11–2Îș1-331323–2436–40++++++No[24]No liganded structure3BNC117, 3BNC60lNR1–2Îș1-33102737–40++++++Yesk[25]Mimics CD4 via CDRH2NIH45–46lIgG11–2Îș3-20163041+++++++Yes[25]No liganded structure12A12, 12A21lNR1–2Îș1-331323–2538–40+++++++Yes[25]8ANC131, 134lNR1–46Îș3-20162737–38+++++Yes[25]1NC9, 1B2530lNR1–46λ1-4716–1924–2636–38+[25]gp120-gp41No liganded structure35O22NR1–18λ2-1416NR35+++++No[46a]No liganded structurePGT151∗NR3–30Îș2D-292818–2227–31+++++No[46b,46c]Peptidoglycan8ANC195∗NR1–69Îș1-5202447+++Yes[25,46d]NR, Not binding characteristics indicated by cocrystal structural analysis. mAb 2G12 utilizes unusual domain swap structure—see indicated references. mAb b12 was isolated from a phase display library, and the natural light chain pair was not retained; b12 displays heavy chain only binding in cocrystal structure with indicates the natural isotype and subclass of the isolated antibody. In some cases, this was not reported. In many cases, the PCR-amplified heavy and light chain genes are expressed in an IgG1 expression vector even if the natural antibody was a different CDRH3 lengths are often based on IMGT or Kabat nomenclature. The Kabat definition is generally used for structural studies and is often 2 AA residues shorter than the IMGT definition. For explanation of the differences in nomenclature, see percentage of mutations nt in an antibody heavy chain is based on comparison with the inferred germ-line gene. Percentage mutation is sometime also reported based on translated AA sequences AA.eNeutralization breadth is indicated for antibodies tested on large panels of >100 tier 2 Env pseudoviruses and the values shown are the percentage of viruses neutralized at an IC50 of <50 ÎŒg/ml. ++++ ≄ 90%; +++ = 75–90%; ++ = 50–74%; + ≀ 50%. If there are several members of a clonal family, the broadest clonal member was potency indicated by median or geometric mean IC50 ÎŒg/ml of neutralized viruses excluding nonneutralized viruses; ++++, IC50 < +++, IC50 = ++, IC50 = +, IC50 = or self-reactivity as assessed by a combination of common autoimmune assays, including cardiolipin ELISA, Hep2 cell IFA, and Athena assay for antinuclear antibody in this clonal lineage, CH03, is have found b12 polyreactive, but studies in b12 VHDJH + VLJL knock-in mice have demonstrated that the degree of polyreactivity for this antibody is not sufficient to predispose these antibodies to tolerance deletion [30].jCH103, CH104, CH106 are autoreactive, CH105 is not is reported to be polyreactive, but 3BNC60 is members of the clonal family also reported in the primary publication. NIH45-45 is same donor and clonal family as VRC01. For mAbs 1NC9 and 1B2530, neutralization data only available for and 02 were initially reported to derive from inferred VK3-11, but additional analysis of the antibody lineages strongly suggests VK3-20. Also, VRC03 was initially inferred to be from different clonal family than VRC01, but more detailed analysis suggests that VRC01, 02 and 03 are clonal relatives Mascola, J and Kwong, P, unpublished observations.Read full chapterURL 1Peter D. Kwong, in Handbook of Cell Signaling Second Edition, 2010Recognition in the Context of a Humoral Immune ResponseAn understanding of the parameters governing HIV-1 receptor interactions would be incomplete without an understanding of the context in which this recognition occurs. While all recognitions pit specific versus non-specific interactions, HIV-1 receptor recognition occurs in the context of a persistent infection. To bind receptor while simultaneously eluding neutralization by the humoral immune system, gp120 has evolved sophisticated strategies of evasion Figure [17, 36–38].Figure Mechanisms of humoral immune trimeric structure of gp120 is depicted in the orientation obtained by optimization of quantifiable surface parameters [40], which is in close agreement with placement based on electron tomogram characterization of HIV-1 viral spikes [41]. The orientation shown depicts the trimer from the viewpoint of the target cell membrane. Core gp120 is depicted with a black Cα worm for inner domain; light gray Cα worm for bridging sheet; gray Cα worm for outer domain; all atom representation for carbohydrate; and semitransparent surfaces for V1/V2-variable loop. Oligomeric shielding of the inner domain by neighboring protomers is apparent, as is the extensive carbohydrate masking of the outer domain surface. The potential shielding of the CD4 binding site by the V1/V2-variable loop is shown with primary mechanisms protect the envelope glycoprotein surface not involved in receptor recognition sequence variation, oligomerization, carbohydrate masking, variable loops, and conformational change. The small size of the HIV genome, coupled to high rates of replication error and recombination, facilitates rapid antigenic escape. Oligomerization uses protein–protein interfaces to block access to conserved epitopes. This protects protein surfaces in both the gp120–gp120 interface as well as the gp120–gp41 interface. Antibodies directed against these surfaces are usually non-neutralizing and recognize only separate gp120 or gp41 components, not the oligomeric gp120/gp41 viral masking involves covering exposed protein surfaces with a dense array of N-linked glycans. Because N-linked glycans are derived from host biochemical pathways, they are interpreted as “self” by the immune system and do not elicit antibodies. In addition, glycans sterically inhibit access to underlying protein surfaces. Epitopes protected by carbohydrate masking are thus immunologically “silent” [37].In terms of the potentially vulnerable receptor-binding surfaces, the virus must recognize receptor, while at the same time eluding an ever-adapting immune response. The surfaces on gp120 that interact with cellular receptors are not only larger than the typical antibody footprint 600 Å2, but also must be functionally conserved and receptor surfaces are partially protected by variable loops. These loops have little structural restraint, and sequence variation can occur at a rate roughly 1,000,000 times faster than the human genome [39]. The CD4 binding site is protected by the V1/V2-variable loop. This loop emanates from the bridging sheet, is approximately 70 amino acids in length, and contains several sites of N-linked glycosylation. Both by steric occlusion and by antigenic variation, the loop shields the CD4 binding site from antibody most conserved exposed surface on gp120 is the bridging sheet, which interacts with both CD4 and co-receptor [17, 23]. HIV hides the conserved bridging sheet through another innovative means, that of conformational change [38]. The bridging sheet is not formed until cell-surface CD4 induces the appropriate structural reorganization in gp120. Such conformational masking serves not only to reduce the elicitation of antibodies against the bridging sheet, but also to prevent neutralization. Within the oligomeric viral spike, quaternary interactions oppose the conformational changes induced by CD4. This opposition decreases the binding efficiency of antibodies that recognize surfaces formed only in the CD4-bound state of gp120. The degree of opposition is controlled by variable loop elements involved in quaternary contact [18]. Extensive variation within these loops allows this opposition to be modulated. With primary isolates, humoral pressures select the degree of opposition to permit only highly avid binding. Because such avidity is available for cell-surface receptors, but not for most antibodies, conformational masking allows HIV-1 to resist neutralization while simultaneously permitting receptor of the HIV-1 receptor interactions illustrates some of the unique features associated with viral receptor recognition. Not only is there the problem of specific binding to receptors; there is also the complementary problem of avoiding specific recognition by the immune system. Compressed into the 500 amino acids of the HIV-1 gp120 are complex mechanisms of evasion and recognition. HIV-1 receptor recognition thus provides an example of a system driven to an extraordinary level of sophistication by the incredible evolutionary speed of HIV-1 opposed by the equally remarkable adaptive capabilities of the immune full chapterURL Delivery System IIRoy Curtiss3rd, in Mucosal Immunology Fourth Edition, 2015New Developments in Antigen Delivery and DisplayGalen et al. 2004 have developed use of the S. Typhi cytolysin A hemolysin as a means to export protective antigens out of the vaccine cells into the supernatant. This was demonstrated using the B. anthracis PA antigen induction of a significantly higher level of immunity after immunization of mice than observed when the PA was not secreted. Baillie et al. 2008 compared delivery of the B. anthracis PA antigen using the HlyA hemolysin and ClyA export system from the licensed S. Typhi Ty21a vaccine using immunization of mice. Delivery of PA via the ClyA system was superior, and the investigators found that the recombinant Ty21a vaccine was very effective in priming a significant immune response to PA administered parenterally at a later and Schifferli 2003, 2007 compared delivery of TGEV spike epitopes as fusion to a subunit of the P987 fimbriae versus using the MisL autotransporter by several attenuated S. Typhimurium strains. Although antibody titers to the S epitopes were higher for the MisL display system, the neutralizing antibody titers were higher for the P987 fimbrial presentation system. Thus, the presentation must have influenced conformation since the MisL fusion construct was synthesized at a times higher level than the P987 fusion T5SS have been investigated for some time as a means to export and present antigens on the cell surface see Curtiss, 2005. All systems have a transmembrane ÎČ-barrel and an external domain that may or may not be cleaved for release by a protease such as OmpT. One can preclude this release by deleting some of the basic amino acids in the hinge region. The Hbp autotransporter studied by Jong et al. 2012 for secretion and display of heterologous antigens in attenuated S. Typhimurium such as ESAT-6 from M. tuberculosis only differs by two amino acids from the autotransporter Tsh that was the first autotransporter identified in the Enterobacteriaceae Provence and Curtiss, 1994. Both Hbp and Tsh bind heme and digest hemoglobin, thus contributing to septicemia caused by ExPEC full chapterURL Kapsidmerupakan selubung terluar (pembungkus) virus yang tersusun atas banyak subunit protein yang dinamakan kapsomer. Dengan adanya kapsid, maka virus dapat berbentuk polihedral, batang, bulat, oval, dan sebagainya. 3. Virus hanya dapat hidup secara parasit pada makhluk hidup sehingga untuk memelihara virus harus digunakan medium berupa a. Agar. b.
Mahasiswa/Alumni Universitas Atma Jaya Yogyakarta23 Juli 2022 1444Jawabannya adalah bertindak sebagai pengunci yang mengikat reseptor pada sel manusia. Salah satu bagian yang terdapat dalam virus adalah protein S atau protein spike. Protein spike berbentuk seperti tonjolan paku yang berada di sekitar permukaan virus. Ketika virus akan menempel ke sel manusia, maka protein spike bertindak sebagai pengunci yang mengikat reseptor pada sel manusia. Proses ini mengakibatkan sel terbuka sehingga virus dapat menginfeksi sel untuk melakukan proses replikasi. Jadi, dapat dikatakan bahwa protein spike adalah pintu masuk virus untuk menginfeksi manusia. Jadi, fungsi protein spike adalah bertindak sebagai pengunci yang mengikat reseptor pada sel manusia.
Virionterdiri atas dua atau tiga bagian: (1) materi genetik, yaitu molekul panjang asam nukleat (berupa DNA saja atau RNA saja, tetapi tidak kombinasi keduanya) yang menyandi struktur protein yang digunakan virus; (2) mantel protein yang disebut kapsid, berfungsi mengelilingi dan melindungi materi genetik; dan pada sebagian virus terdapat (3) selubung atau amplop luar yang terbuat dari lipid. Pengertian Virus Virus adalah parasit berukuran mikroskopik yang menginfeksi sel organisme biologis. Virus dibedakan dari agen infeksius yang lain, karena ukurannya yang kecil dapat melewati membran filter bakteri serta sifatnya sebagai parasit intraseluler obligat, yang mutlak memerlukan sel inang untuk hidup, tumbuh, dan bermultiplikasi. Virus hanya dapat bereproduksi di dalam material hidup dengan menginvasi dan memanfaatkan sel makhluk hidup karena virus tidak memiliki perlengkapan selular untuk bereproduksi sendiri. Biasanya virus mengandung sejumlah kecil asam nukleat yang diselubungi semacam bahan pelindung yang terdiri atas protein, lipid, glikoprotein, atau kombinasi ketiganya. Genom virus menyandi baik protein yang digunakan untuk memuat bahan genetik maupun protein yang dibutuhkan dalam daur hidupnya. Virus merupakan kesatuan yang mengandung asam nukleat DNA atau RNA dan mengandung protein selubung coat protein. Kadang virus tertutup oleh envelope dari lipid, protein, dan karbohidrat yang mengelilingi asam nukleat virus. Virus mungkin juga memiliki membran lipid bilayer atau kapsul tapi diperoleh dari sel inang, biasanya dengan tunas melalui membran sel inang. Jika terdapat membran, virus berisi satu atau lebih protein virus untuk bertindak sebagai ligan untuk reseptor pada sel inang. Perbedaan Virus dan Bakteri No Karakteristik Bakteri Umum Bakteri Chlamedia Virus 1 Parasit intraseluler - v v 2 Membran plasma v v - 3 Pembelahan biner v v - 4 Melewati filter bakteri - v/- v 5 Memiliki DNA & RNA sekaligus v v - 6 Metabolisme menghasilkan ATP v v/- - 7 Ribosom v v - 8 Sensitivitas terhadap antibiotik v v - 9 Sensitivitas terhadap interferon - - v Virus menginfeksi semua kelompok organisme utama, vertebrata, invertebrata, tumbuhan, jamur, bakteri, tetapi beberapa virus memiliki kisaran inang yang lebih luas daripada yang lain, namun tidak dapat menembus batas eukariotik/prokariotik. Permukaan virus berinteraksi dengan reseptor spesifik dan permukaan sel inang dengan pengikatan hidrogen. Virion merupakan partikel virus yang lengkap, sempurna, dan telah berkembang penuh serta bersifat infeksius. Virion tersusun atas asam nukleat dan dikelilingi oleh protein selubung coat protein yang melindungi dari lingkungan sekelilingnya. Virion juga dilengkapi peralatan untuk transmisi dari satu sel inang ke sel inang yang lain. Beberapa virus menyandi sedikit protein struktural hal ini yang membentuk partikel virus matang atau virion dan mungkin enzim yang berpartisipasi dalam replikasi genom virus. Virus lainnya dapat mengkode lebih banyak protein, yang sebagian besar tidak berakhir pada virus matur tetapi berpartisipasi dalam berbagai replikasi virus. Virus herpes adalah salah satu virus yang lebih rumit dan memiliki 90 gen. Karena banyak virus membuat sedikit atau tidak ada enzim, mereka tergantung pada enzim sel inang untuk menghasilkan lebih banyak partikel virus. Dengan demikian, struktur virus dan replikasi pada dasarnya berbeda dari organisme selular. Ketergantungan virus pada sel inang terhadap berbagai aspek siklus pertumbuhan merumitkan pengembangan obat karena kebanyakan obat akan menghambat pertumbuhan sel serta multiplikasi virus karena beberapa enzim sel yang digunakan. Alasan utama untuk mempelajari metabolisme virus adalah untuk menemukan obat yang selektif menghambat perbanyakan virus, kita perlu tahu kapan virus menggunakan proteinnya sendiri untuk siklus replikasi, kemudian dapat mencoba untuk mengembangkan obat yang menghambat protein virus terutama enzim virus secara khusus. Struktur Virus Rentang ukuran virus dari diameter 20 nanometer, seperti Parvoviridae, sampai beberapa ratus nanometer panjangnya, seperti Filoviridae. Semua virus mengandung genom asam nukleat RNA atau DNA dan selaput protein pelindung/coat protein disebut kapsid. Asam nukleat virus berupa DNA atau RNA, beruntai tunggal/single strand ss, ataupun beruntai ganda/double strand ds, sehingga dikenal dengan kelompok virus ssRNA, dsRNA, ssDNA, dan dsDNA. Asam nukleat virus dapat berbentuk linear maupun sirkuler. Kapsid coat protein adalah susunan protein yang mengelilingi asam nukleat virus. Struktur kapsid sangat ditentukan oleh asam nukleat virus. Kapsid tersusun atas subunit-subunit protein yang disebut kapsomer. Genom asam nukleat ditambah selaput protein pelindung yang disebut nukleokapsid yang mungkin memiliki ikosahedral, heliks, atau kompleks simetri. Pada beberapa virus, kapsid ditutupi oleh sampul envelope yang umumnya terdiri atas kombinasi antara lipid, protein, dan karbohidrat. Sampul atau selaput envelope dapat ditutupi oleh struktur serupa paku spike yang merupakan kompleks karbohidrat protein. Virus mendapatkan pembungkus dengan tunas melalui membran sel inang. Spike berperan pada proses perlekatan virus pada sel inang. Virus dengan kapsid yang tidak tertutup envelop disebut virus telanjang non envelope virus. Pada virus ini, kapsid melindungi asam nukleat virus dari enzim nuklease dalam cairan biologis inang dan mendukung perlekatan virus pada sel inang yang peka. Morfologi Virus Gambar Bentuk heliks, icosahedral, dan kompleks pada virus Salvo, 2012 Terdapat beberapa tipe virus berdasarkan arsitektur kapsidnya. Virus Heliks - Subunit protein dapat berinteraksi satu sama lain dan dengan asam nukleat membentuk melingkar, struktur seperti pita. Virus yang dipelajari dengan heliks simetri terbaik adalah virus tanaman non-envelop, virus mosaik tembakau. Sifat heliks virus ini cukup jelas dalam mikrograf elektron pewarnaan negatif karena virus membentuk struktur seperti batang kaku. Virus Polihedral - Virus ini terdiri atas banyak sisi, kapsid berbentuk ikosahedron, polihedron reguler dengan 20 permukaan triangular dan 20 sudut. Contoh adenovirus, poli virus. Virus Bersampul enveloped - Virus berbentuk bulat. Bila virus heliks dan polihedral ditutupi oleh envelope, maka virus ini disebut virus heliks bersampul atau virus pihedral bersampul. Contoh virus ini adalah virus influenza, virus rabies, dan virus herpes simpleks polihedral bersampul. Virus kompleks - Memiliki struktur yang kompleks, contoh bakterifage, kapsid berbentuk polihedral dengan tail sheat berbentuk heliks dan poxovirus, kapsid berbentuk tidak jelas dengan protein selubung coat protein di sekeliling asam nukleat. Taksonomi Virus Para peneliti virus membuat sistem klasifikasi virus, dengan membentuk komite internasional taksonomi virus International Committee on the Taxonomy of Viruses/ICTV pada tahun 1966. ICTV mengelompokkan virus menjadi beberapa famili suku berdasarkan Tipe asam nukleat Strategi replikasi Morfologi Akhiran - virus - digunakan untuk genus marga, nama famili suku berakhiran dengan viridae, dan nama ordo bangsa berakhiran ales. Reproduksi Virus Virus hanya dapat berkembang biak pada sel atau jaringan hidup. Oleh karena itu, virus menginfeksi sel bakteri, sel hewan, atau sel tumbuhan untuk bereproduksi. Cara reproduksi virus disebut proliferasi atau replikasi. Gambar Bakteriofag Salvo, 2012 Tahapan multiplikasi virus terdiri atas Adsorpsi penyerapan - Merupakan interaksi spesifik virus dan inang. Terdapat reseptor khusus yang memperantarai pengenalan virus oleh sel inang. Ligan pada virus akan dikenali oleh reseptor ada inang dan menempel pada reseptor sel inang dapat berupa pili, flagella, komponen membran atau protein pengikat pada bakteriofag. Pada virus influenza, ligan berupa glikoprotein dan pada eritrosit dan virus polio, ligan berupa lipoprotein. Perasukan dan pelepasan selubung - Merupakan tahap lanjut setelah virus menempel pada permukaan sel inang. Pada bakteriofag, perasukan berlangsung melalui ekor fag yang berkontraksi sehingga terjadi cengkraman pada bagian ekor membran sel bakteri. Selaput ekor berkontraksi dan DNA virus masuk melalui pori-pori pada ujung ekor. Replikasi dan sintesis komponen virus - Bagi virus DNA didahului dengan replikasi DNA, sedangkan pada virus RNA didahului dengan complementary DNA cDNA. Perakitan - Pada virus DNA berlangsung di dalam nukleus, sedangkan pada virus RNA berlangsung dalam sitoplasma sel inang. Pelepasan - Dapat melalui lisis pecahnya sel ataupun fagositosis dengan mekanisme yang berlawanan virus dilepas melalui pertunasan pada bagian tertentu membran sel. Bakteriofag yang merupakan virus penginfeksi bakteri. Pada Bakteriofage reproduksinya dibedakan menjadi dua macam, yaitu daur litik dan daur lisogenik. Replikasi tersebut baru dapat dilakukan ketika virus ini telah masuk ke dalam sel inangnyabakteri. Gambar Siklus Bakteriofag Salvo, 2012 Pada daur litik, virus akan menghancurkan sel induk setelah berhasil melakukan reproduksi. Sedangkan pada daur lisogenik, virus tidak menghancurkan sel bakteri tetapi virus berintegrasi dengan DNA sel bakteri, sehingga jika bakteri membelah atau berkembangbiak virus pun ikut membelah. Pada prinsipnya cara perkembangbiakan virus pada hewan maupun pada tumbuhan mirip dengan yang berlangsung pada bakteriofage, yaitu melalui fase adsorpsi, sintesis, dan lisis. Bakteriofag termasuk ke dalam ordo Caudovirales. Salah satu contoh bakteriofag adalah T4 virus yang menyerang bakteri Eschericia coli E. coli, merupakan bakteri yang hidup pada saluran pencernaan manusia. Perbedaan virus dengan bakteriofag adalah bahwa virus hidup dan berkembang biak baik dalam mikroorganisme yang multisel, sedangkan bakteriofag hidup dan berkembang biak dalam organisme satu sel.

Virustersusun atas materi inti yang mengandung asam nukleat. Coronavirus Disease Covid-19 Tubuh tersusun dari asam nukleat b. Spike pada virus tersusun atas protein dan karbohidrat yang disebut. Soal dan pembahasan

When the TGEV spike protein binds to EGFR, it sets in motion the microfilaments’ polymerization by activating an intracellular signaling pathway that involves phosphoinositide-3 kinase and Rac1/Cdc42 GTPases as well as the ERK MAPK Pathogenic Coronaviruses of Humans and Animals, 2023Natural Protein FibersC. Viney, in Encyclopedia of Materials Science and Technology, Viral Spike ProteinThe structural characteristics of virus coats capsids are highly relevant to virus propagation, and are therefore the subject of intensive study. The coat must contain and protect the nucleic acid genetic contents, be resilient against impact, be capable of broaching the outer wall of a target cell, and provide a secure pathway for conducting nucleic acid into the target. Hollow spikes on the capsid fulfill the latter two roles, from which it has been deduced that they must have unusually high strength and stiffness in axial compression. Because compressive strength and stiffness have been a long-term but elusive goal of polymer science, the hierarchical structure of spike proteins deserves careful attention.a Cross-ÎČ-sheetsViral spike protein contains several repeats of relatively short ÎČ-strand-forming amino acid sequences. The chain folds back and forth to assemble a ÎČ-sheet, stabilized by intramolecular hydrogen bonds Fig. 2. Because the long axis of the sheet is transverse rather than parallel to the molecular backbone, the structure in this case is known as a cross-ÎČ-sheet. Some silks, the egg stalks of green lacewing flies, are also reinforced by cross-ÎČ-sheet crystals.b Higher-order structureThe structure varies significantly between different virus types. For both rotavirus and human adenovirus, there is evidence that three cross-ÎČ-sheets interact to form a hollow trimeric box beam that resists buckling in compression. Structural characterization is hampered by the small size of individual spikes lengthâ©œ30 nm and widthâ©œ5 nm. Hydrophobic bonding is presumed to be important in stabilizing their structure, since 70% of the amino acid residues are hydrophobic in representative engineered model polymers, based on multiple consecutive copies of the principal repeated sequence in native adenovirus spike protein, can self-assemble into a liquid crystalline phase in solution. However, trimeric box beams have not been found in the hierarchical microstructure of fibers spun from this phase. The spun fibers are formed under significantly off-equilibrium conditions, and should not be expected to have the same internal structure as the native spikes.c PropertiesIn tensile tests conducted on dry fiber, the breaking strength is ∌ GPa, the stiffness ∌4 GPa, and the elongation to failure ∌ 30%. Given the evidence that the native spikes rely on hydrophobic bonding to maintain their structure, the properties of analog fibers as measured in air are likely to be inferior compared to results obtained in water—even if the detailed microstructure of the native material could be reproduced. In other words, the natural material is designed to work in an aqueous medium, and attempts to mimic its properties must take this reality into full chapterURL nanomaterials for infectious diseasesArchita Jha, Yashwant Pathak, in Nanotheranostics for Treatment and Diagnosis of Infectious Diseases, HydrogelThe SARS-CoV-2 Virus spike proteins contain a receptor-binding domain RBD for attachment and entry into the host cell. Recombinant RBD can induce a neutralizing antibody response that can bind to the SARS-Cov-2 RBD thus inhibiting the infection cycle [70]. Being cost-effective and amenable to large-scale manufacturing, subunit vaccines containing the recombinant RBD antigen provide beneficial value in global vaccine distribution efforts. Injectable polymer-nanoparticle PNP hydrogel structures with de-risked adjuvants CpG and Alum provide efficient vaccine delivery methods with enhanced immunogenicity of RBD. The hydrogel along with alum is beneficial and allows for a controlled and slow release of the vaccine over a span of 10–18 days, eliminating the need for booster shots. Additionally, polymer-nanoparticles hydrogels allow for the loading of various components of the vaccine such as the RBD, alum, and CpG to be co-delivered. The IgG antibody titers, utilized as markers for the immune response by RBD and adjuvants in PNP hydrogels, were 60 times greater than utilizing other adjuvants or RBD by itself [71]. Overall, hydrogels utilized for subunit vaccines have displayed promising results and ensured widespread vaccine full chapterURL Methods in Protein Biochemistry Part AMax Meyrath, ... on behalf of the CON-VINCE Consortium, in Methods in Enzymology, 20222 Before you beginThis virus-free assay uses two cell lines expressing respectively the viral spike and host cell receptor ACE2 on their surface and builds on the principle that cell membranes merge upon spike-ACE2 interaction. Each cell line additionally expresses one part of the NanoLuc luciferase HiBiT or LgBiT that on their own do not emit light, but when brought together, quickly self-complement due to their high affinity for each other to reconstitute a fully functional NanoLuc HiBiT technology, Promega. When co-incubated, these two cell lines are able to form syncytia through their cell membrane fusion facilitated by the spike-ACE2 interaction, in turn allowing rapid and spontaneous complementation of the cytoplasmic NanoLuc fragments and giving rise to ultra-bright bioluminescence in the presence of a specific substrate Fig. 1. Similar to classical viral neutralization assays, pre-incubation with neutralizing antibodies blocking the spike-ACE2 interaction prevents syncytia formation, which can be titrated and quantified by measuring the reduced light emission in comparison to cells that were not treated with neutralizing antibodies Fig. 1A and C.Fig. 1. Cell fusion assay based on high-affinity NanoLuc complementation HiBiT A Schematic representation of the assay set-up. LgBiT and spike-expressing HEK293T cells are mixed with HiBiT- and ACE2-expressing Vero E6 cells and co-incubated overnight. Upon spike interaction with ACE2, cell membranes merge, forming a multinucleated syncytium and enabling complementation of both NanoLuc fragments, eventually leading to light emission upon substrate addition. Pre-incubation of spike-expressing cells with neutralizing antibodies will prevent the spike–ACE2 interaction and limit syncytia formation. Multiple sera can be tested simultaneously in 96- or 384-well format, enabling high-throughput screening of samples. B Representative microscopy pictures, illustrating syncytium formation between Vero E6 cells expressing an mKOrange-tagged membrane marker and HEK293T cells expressing a NeonGreen cytoplasmic marker. DAPI-stained nuclei are depicted in blue. C Representative picture of a 96-well plate after substrate addition taken with an ordinary mobile phone camera Huawei p20 Pro. The intense blue bioluminescent signal emitted by the NanoLuc is well visible even with the naked eye. No light is emitted from wells where cells did not efficiently form syncytia, indicative of the presence of neutralizing A Figure was created using the material, vectors and protocols described below, this “SARScytium” assay can easily and reproducibly be performed using transiently transfected cells, where one cell line is transfected with viral spike and LgBiT, whereas the other cell line is transfected with HiBiT and ACE2 Fig. 1A. The approach using transient transfections allows for high versatility and flexibility of the assay with easy and fast adaptability to spike variants. This can be of particular interest given that the antibody neutralization profile considerably varies between the different spike variants and the high probability of emergence of new variants Duarte et al., 2022; Harvey et al., 2021. Alternatively, cells stably expressing the required proteins can be used. This accounts especially for ACE2, where a variety of cells stably expressing ACE2 are commercially available, such as Vero E6 cells that endogenously express ACE2, or HEK or HeLa cells exogenously overexpressing ACE2 together or not with the protease TMPRSS2 that serves as a co-factor for SARS-CoV-2 infection and is implicated in spike priming on the full chapterURL coronavirus infections of the lower respiratory tract and their preventionN. Petrovsky, in The Microbiology of Respiratory System Infections, 20163 Recombinant spike protein vaccinesA major advance in vaccine development was the identification that the SARS virus spike S protein mediates cell entry via its ability to bind angiotensin-converting enzyme 2 and CD209L, thereby triggering virus endocytosis into target A human monoclonal antibody binding the S protein N-terminal domain was shown to be able to block infection, thereby identifying S protein as a major target of SARS virus neutralizing Consistent with this, monkeys could be protected against SARS infection by intranasal immunization with a S protein-encoding live parainfluenza S protein was also shown to be the target of CD4 and CD8 T cell responses suggesting these may also be important to SARS A recombinant S protein vaccine was manufactured using an insect cell expression system but was found to be considerably less immunogenic that inactivated whole virus vaccine, requiring ∌100 times more antigen to achieve the same level of Attempts to improve the immunogenicity of S protein vaccine by formulation with alum adjuvant again resulted in severe lung eosinophilic immunopathology in response to SARS virus infection, marking this as another potentially unsafe This confirmed that the problem of lung eosinophilic immunopathology was not just confined to inactivated or nucleocapsid protein vaccines but was a more general problem of vaccines made from any SARS virus full chapterURL in respiratory systemMd Bashir Uddin, ... Syed Sayeem Uddin Ahmed, in Recent Advancements in Microbial Diversity, SARS virusesACE2 angiotensin-converting enzyme 2 acts as the SARS viral spike glycoprotein binding receptor, allowing the virus to adhere to host cells and then internalize and replicate Hoffmann et al., 2020; Liu et al., 2020; Yan et al., 2020. However, respiratory tract macrophages and DCs, all essential immune system cells, express ACE2 Keidar et al., 2005. As shown by the influenza, herpes, and Zika viruses, viral infections induce monocytic-enhanced proinflammatory signaling molecules and antiviral responses Nikitina, Larionova, Choinzonov, & Kzhyshkowska, 2018. It has recently been suggested that increased development of proinflammatory macrophages in a subset of COVID-19 patients contributes to an increase in the production of inflammatory cytokines and chemokines, like CXCL10, which causes cytokine storms. This has been found mostly in subjects with a low prognosis Vaninov, 2020; Yang et al., 2020. In general, short-lived monocytes/macrophages will significantly restrict viral replication. Nevertheless, this does not rule out the likelihood of these cells acting as a permissive mechanism and/or a viral reservoir Nikitina et al., 2018. The fact that these cells are the first line of protection against viral infection lends credence to this theory. However, viral infection has the potential to transform these cells into long-living macrophages M and facilitate their migration into tissues where they become infected resident cells. Finally, since SARS viruses, like SARS-CoV-2, use ACE2 as a tight, high-affinity binding site Hoffmann et al., 2020; Liu et al., 2020; Yan et al., 2020. ACE2-expressing pulmonary macrophages can permeate pulmonary invasion during SARS infection. Indeed, we previously demonstrated that monocytes and macrophages release ACE2 Keidar et al., 2005.Interestingly, macrophages also release furin and TMPRSS2, two enzymes implicated in the interaction of the SARS virus’s attachment and effusion sites Bertram et al., 2010; Gagnon et al., 2013 and ADAM 17, which acts as sheddase of ACE2 Nikolaidis et al., 2010. In the presence of both viral binding and activation components, the virus will potentially replicate in human macrophages and DCs, causing abnormal development of proinflammatory cytokines/chemokines, as is the case with MERS-CoV Zhou, Chu, Chan, & Yuen, 2015. Some experiments, on the other hand, have ruled out SARS-CoV viral replication in human macrophages Yilla et al., 2005. Despite abortive infection, which is described as infection without replication, SARS-CoV infection of human macrophages resulted in the expression of proinflammatory chemokines but not antiviral cytokine output Lee et al., 2009; Tseng, Perrone, Zhu, Makino, & Peters, 2005. COVID-19 morbidity and mortality are markedly amplified in definite populations, namely aged and diabetic patients with COPD or congestive heart failure CHF Perico, Benigni, & Remuzzi, 2020, and perhaps among patients on inhibitors of the renin-angiotensin aldosterone system RAAS Fang, Karakiulakis, & Roth, 2020; Perico et al., 2020. These explanations might be related with bigger numbers of AMs in such patients or alterations in the AM phenotype. Indeed, increased numbers of AM in bronchoalveolar lavage BAL were noticed in humans with COPD in proportion to their disease severity AgustĂ­ & Hogg, 2019.Read full chapterURL VaccinesJaap W. Back, Johannes Langedijk, in Advances in Immunology, 20122 Stabilizing AntigensThe detailed structural knowledge on many neutralization sites, the location of some conserved exposed surfaces on the native viral spike, and the general architecture and dynamics of the labile structure reveals some clues of how to stabilize the spike in order to induce such broadly neutralizing way of using the structural knowledge for a recombinant protein-based vaccine is to engineer, modify, or stabilize the labile spike in such a way that the recombinant soluble protein mimics the prefusion native trimer that can cross-react with all the broadly neutralizing antibodies and remains stable in a vaccine adjuvant. Several approaches have been applied successfully to stabilize the case the immunogen is based on the soluble envelope protein, the deletion of the membrane anchor destabilizes the trimer which can be compensated by inclusion of heterologous trimerization domains Yang et al., 2000. Additionally, the prefusion conformation can be stabilized by preventing the FP from swinging out and the gp120 head to detach. A straightforward solution to fix the FP in its prefusion position and obstruct the refolding of gp41 into the stable postfusion conformation is to prevent the cleavage of the precursor gp160 into mature gp120–gp41 heterodimer Yang et al., 2000. Alternatively, to increase the chance of maintaining the FP in its native, probably buried, position, gp120 and gp41 can be covalently linked by the introduction of an intermolecular disulfide bridge Binley et al., 2000; Yang et al., 2000. Although it has been possible to engineer a disulfide with trial and error, high-resolution detail of the structure would permit rational introduction of stabilizing disulfide bonds that connect the heterodimer. Disulfide bridges have also been used for the intramolecular stabilization of the flexible regions within the subunits Dey et al., 2009; Zhou et al., 2007. Constructing a heat-stable foot-and-mouth disease vaccine by disulfide engineering came within reach when the crystal structure of the viral capsid was solved Mateo et al., 2008 and also the atomic-level resolution of the complete prefusion spike of HIV will undoubtedly contribute to structure-based design of inter- and intramolecular disulfides without going through the arduous path of trial and full chapterURL Cellular Phagocytosis and Its Impact on Pathogen ControlStefan S. Weber, Annette Oxenius, in Antibody Fc, 2014Targeting of Viruses to FcRsViral infection of target cells in the absence of virus-specific antibodies is in general dependent on the interaction between viral spike proteins and corresponding receptors on target cells, thereby conferring a specific tropism of individual viruses to their target cells. Antibody-opsonized virus particles, however, may gain access to additional FcR-expressing target cells. Uptake of opsonized virus particles into FcR-bearing phagocytes via FcR-dependent phagocytosis may have different outcomes for the infection process and for the ensuing spread and control of the virus infection. While very little is known about the exact intracellular fate of opsonized virus particles and how this relates to their infectivity in phagocytes, most available data indicate that FcR-mediated uptake into phagocytes does not interfere with intracellular viral replication. However, in situations when opsonizing antibodies have direct neutralizing effects on the fusion or uncoating process of the virus, and when this property is maintained under acidic conditions as present in late phagosomes/lysosomes,106–108 FcR-mediated uptake of opsonized viruses might restrict replication within phagocytes. In cases where the infected phagocyte does not support the requirements of a specific viral life cycle, FcR-mediated uptake of opsonized viruses may also lead to enhanced control of viral full chapterURL Treatment and Prevention of Virus InfectionsGuangdi Li, ... Erik De Clercq, in Encyclopedia of Virology Fourth Edition, 2021HIV GP41GP41 is a transmembrane protein encoded by the env gene. As a key structure protein, HIV GP41 binds with GP120 to form HIV spike trimers on the surface of HIV particles Mao et al., 2012. During the viral entry, the N-heptad repeat NHR and C-heptad repeat CHR of GP41 switch to a six-helix bundle 6-HB structure which binds to the human cell membrane and drives the viral fusion into the human cells. Many antiviral agents have been developed to target the hydrophobic pocket within the NHR trimer, therefore preventing viral entry Mostashari Rad et al., 2018.As the only GP41 inhibitor approved by the US FDA, enfuvirtide is a fusion peptide inhibitor that mimics the N-heptad repeat and prevents the formation of the six-helix bundle structure of GP41. Clinical use of enfuvirtide requires twice-daily subcutaneous injection 90 mg/Kg for adults, 2 mg/Kg for children aged 6–16 years Kitchen et al., 2008. Enfuvirtide is not commonly used in clinical practice because of its side effects eosinophilia, neutropenia, increased risk of bacterial pneumonia, its short half-life, and lack of oral availability Reust, 2011. Although many attempts have been made, the development of GP41 inhibitors remains difficult due to the emerging mutations and structural dynamics of HIV full chapterURL repurposing existing vaccines and antibiotics help to control the COVID-19 pandemic?Kajal Rathod, ... Buddolla Viswanath, in Pandemic Outbreaks in the 21st Century, Therapeutic targets‱Coronaviruses inhibit antiviral immunity, allowing interferons IFNs to sustain an antiviral state.‱The virus moves into the cell by fusing viral spike proteins with the cellular ACE2 receptor, which causes ACE2 to be downregulated. Angiotensin receptor blockers and angiotensin-converting enzyme inhibitors and statins increase ACE2 expression, thereby having better efficacy.‱The virus is then endocytosed, with low endosomal pH assisting in the lysis of viral structural proteins. The antiviral action of diprotic bases like chloroquine and hydroxychloroquine may disrupt the acidic environment.‱Nucleic acid NA is released into the cytoplasm.‱Translation of viral proteins with help of the host ribosomes.‱Viral protease enzyme undergoes proteolysis to form functional proteins, for example, RDRP. Inhibitors such as lopinavir, ritonavir, and darunavir may thus be effective against the virus by inhibiting the key protease enzyme.‱The replication and transcription of viruses are dependent on the presence of RDRP. Coronaviruses may be prone to RDRP inhibitors including remdesivir, favipiravir, ribavirin, and arbidol. Virions are formed after subsequent translation, proteolysis, and packaging of proteins, which are then exocytosed out of the full chapterURL 2Saul O. Lugo Reyes, Armando Partida GaytĂĄn, in Allergic and Immunologic Diseases, 2022COVID-19 vaccines as gene therapiesSome vaccines to prevent SARS-CoV-2 infection or disease employ messenger RNA Pfizer-BioNTech, Moderna delivered by NPs to transmit our cells the transcript code to manufacture the infamous spike viral glycoprotein or its receptor-binding domain RBD. Other vaccines Oxford-AstraZeneca, Beth Israel-Johnson&Johnson employ a nonreplicating adenoviral vector, from a virus that normally infects chimpanzees, with good results [35]. Some scholars consider these to be gene therapies, even though these vaccines cannot alter human DNA or change our genes. Messenger RNA will not enter the nucleus but will instead stop at the cell ribosomes to deliver the message. No hematologic malignant transformations are expected to occur for the same reason. NP-delivered mRNA and adenoviral vectors are simply clever ways to develop vaccines using gene therapy-based principles or techniques [36].Nevertheless, as for any vaccines and any drugs or injectable biologic agents, safety trials are underway to assess any long-term adverse effects. Given the circumstances of the pandemic, all four vaccines were “fast-tracked” and approved for emergency use, but only after they completed all the safety and efficacy full chapterURL
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    • spike pada virus tersusun atas protein dan karbohidrat yang disebut