Surface of Enveloped Viruses
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1 Surface of Enveloped Viruses Ye, Rong Ph.D. Fudan University School of Basic Medical Sciences
2 1. Introduction: Diversity of viruses and viral surfaces 2. Membrane fusion: A critical step of viral entry into the cell 3. Membrane budding: A major mode for the assembly of viral envelopes 4. Host receptor: A determinant of viral transmission
3 烟草花叶病毒 Tobacco Mosaic Virus Stanley 1935 年
4 Host and Genome of Viruses Genome types General Host Algae Archaea Bacteria Fungi Invertebrates Plants Protozoa Vertebrates DNA viruses: dsdna viruses ssdna viruses ReverseTranscriptase: dsdna-rt viruses ssrna-rt viruses RNA Viruses: dsrna viruses (-)ssrna viruses (+)ssrna viruses
5 Reports of the International Committee on Taxonomy of Viruses
6 感染细菌的病毒
7 感染人类和 动物的病毒
8 感染植物的 病毒
9 感染昆虫的病毒
10 Hosts of viral infection
11 Structural difference of animal and plant viruses
12 Naked Viruses Adenovirus Tobacco Mosaic Virus
13 Enveloped viruses HBV HIV Ebola Virus
14 1. Introduction: Diversity of viruses and viral surfaces 2. Membrane fusion: A critical step of viral entry into the cell 3. Membrane budding: A major mode of the assembly of viral envelopes 4. Host receptor: A determinant of viral transmission
15 Life Cycle release Coronaviruses entry secretary vesicle coated vesicle endosome Golgi decapsidation genomic RNA 1a/1b (rdrp) (-) strand RNA 2 3 genomic RNA (RNA1) ERGIC subgenomic RNAs HE S E M N nucleocapsids translocation co-translation 1 Nucleus ER
16 Class I fusion proteins Orthomyxovirus: HA0 HA1+HA2 (Influenza) Paramyxovirus: F0 F1+F2 (Measles, NDV, Sendai, RSV) Retrovirus: gp160 gp120+gp41 (HIV) Coronavirus: S S1+S2 (MHV) Filovirus: GP GP1+GP2 (Ebola) HA1 HA2 Tm+E d 正粘病毒 gp120 gp41 Tm+E d 逆转录病毒 S1 S2 Tm+E d 冠状病毒
17 Class l Membrane Fusion 6-Helix Bundle RSV HIV flu SV5
18 Class II fusion proteins Flaviviruses: E protein (Dengue, YF, TBE, WN) Alphaviruses: E1 protein (Sindbis, Semliki Forest)
19 Genes and proteins of Flavivirus
20 E protein of Flavivirus
21 Transformation of E protein
22 Class III fusion proteins
23 FAST Proteins of Reoviruses (Fusion-associated Small Transmembrane)
24 Cartoon show: Inhibition of membrane fusion : A new target for antiviral therapy
25 Membrane fusion
26 Fusion inhibition
27 Homework-1 Stephen, C. Harrison (2008) : Viral membrane fusion. Nat. Struct. & Mol. Biol. 15,
28 1. Introduction: Diversity of viruses and viral surfaces 2. Membrane fusion: A critical step of viral entry into the cell 3. Membrane budding: A major mode for the assembly of viral envelopes 4. Host receptor: A determinant of viral transmission
29 Cells and viral replication
30 Trafficking of cellular and viral Proteins
31 Genes and proteins of HIV
32 HIV Entry to and release from cells
33 MVB and ESCRT Multivesicular bodies (MVBs) and endosomal sorting complex required for transport (ESCRT)
34 Gag and HIV Assembly
35 Genes and Proteins of Influenza Virus PB2 RNA 聚合酶成分 PB1 RNA 聚合酶成分 PA RNA 聚合酶成分 HA 与黏附, 融合等有关 NP 核衣壳蛋白 NA 分解唾液酸 M1 基质蛋白, 包膜和核蛋白 M2 膜蛋白, 离子通道蛋白 NS1 非结构蛋白, 抑制 mrna NS2 非结构蛋白, 功能不清楚
36 Membrane Scission of Influenza Virus
37 Homework-2 J.B. Rossman, X. Jing, G.P.Leser and R.A. Lamb Influenza Virus M2 Protein Mediates ESCRT-Independent Membrane Scission CELL 142, , 2010
38 Lipid Rafts
39 MA protein interacts with lipids
40 Myristoylation of HBV and HDV pres1 L M S H. Yan, et al., (2012) Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. elife,1:e00049
41 Palmitoylation of MHV S protein J. Yang, et al., (2012) Replication of murine coronavirus requires multiple cysteines in the endodomain of spike protein. Virology 427,
42 1. Introduction: Diversity of viruses and viral surfaces 2. Membrane fusion: A critical step of viral entry into the cell 3. Membrane budding: A major mode of the assembly of viral envelopes 4. Host receptor: A determinant of viral transmission
43 Diversity of Viral Receptors CD4 Icam-1 CD21 CD13, ACE2 CD81/LDLR Sialic acids Pvr CD55,Val-2,Vitronectin R Heparin Sulfate CD46 HIV1, HHV7 Rhino- EB Conona- Hepatitis C Influenza, Reo-, et al. Polio- Entero- HSV-1,-2, CMV, Dengue, Sindbis, Vaccinia Measles
44 Specificity of Viral receptor Coronavirus receptor H 高特异性受体 CEACAMs (Carcinoembryonic antigen-related cell adhesion molecules): MHV ACE2 (Angiotensin-converting enzyme 2 ):SARS-CoV and HCoV-NL63 DPP4 (dipeptidyl peptidase 4): HCoV-EMC M 中等特异性受体 APN (Aminopeptidase N): Human APN:HCoV-229E Porcine APN:TGEV Canine APN:CCoV Feline APN:FCoV Alpha-coronaviruses L 低特异性受体 DC-SIGN: the calcium-dependent (C-type) lectin dendritic cell-specific intercellular adhesion molecule- 3 grabbing non-integrin (CD209) L-SIGN (DC-SIGNR): DC-SIGN related protein (CD299)
45 HIV Co-receptor: CXCR4 and CCR5
46 Viroceptor and Virokine Virus-encoded homolog of cellular receptors of cytokines Vaccinia virus-b8r/b18r: receptor for IFN-γ/α Cowpox virus-crmb/d: binding to TNFα/β, LT-α Variola virus-vckbp: binding to virious chemokines Human herpesvirus-6-u12/u51: binding to various chemokines Epstein-Barr virus-barf1: binding to M-CSF Maxoma virus-t2/t7: binding to IFNγ/ β Cytomegalovirus-US28: binding to various chemokines Virus-encoded mimics of host cytokine Small and powerful immune proteins Possess immunosubversive activities These viral genes are from host cells Vaccinia virus-19 kda protein: EGF Cowpox virus-38k gene: Inhibitor of IL1βConvertase KSHV: Viral IL6/Viral MIP-1,2,3 Epstein-Barr virus-bcrf1: viral IL10 Maxoma virus-serp1/2:inhibitor of IL1βConvertase Cytomegalovirus-CMV IL10 Orf virus-14.7/16 kda protein: VEGF HIV-tat protein: VEGF, integrin, chemokines
47 Coronavirus and S protein RBD
48 SARS: ,098 case 774 deaths 25 countries
49 WHO: Global Alert and Response Dr. Carlo Urbani February 2003 Hanoi, Vietnam 2012(5,73)
50 SARS Time-Course The Chinese SARS Molecular Epidemiology Consortium (2004) Science 303,
51 Molecular evolution of SARS-CoV
52 Variation of S protein RBD
53 Adaptation of SARS Coronavirus to Humans
54 Transmission of Coronaviruses
55 总结 病毒表面结构呈现多样性, 分为有包膜和无包膜病毒 病毒包膜主要由膜蛋白和脂质层构成, 其结构与功能密切相关 病毒表面包膜主要有三个主要功能 : 结合受体决定病毒的宿主特异性 ; 通过构象变化实现膜融合 ; 定位膜表面, 启动病毒粒子装配与释放 病毒表面膜蛋白采用类似于细胞固有的一些机制实现其功能, 并具有进化适应的的能力
56 Thank you!
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