surface of enveloped viruses - fudan university · 2013. 9. 13. · surface of enveloped viruses...
TRANSCRIPT
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Surface of Enveloped Viruses
Ye, Rong Ph.D.
Fudan University School of Basic Medical Sciences
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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
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烟草花叶病毒Tobacco Mosaic Virus
Stanley
1935年
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Host and Genome of Viruses
General Host
Algae ArchaeaBacteria
FungiInvertebrates
Plants Protozoa
Vertebrates
Genome types
DNA viruses: dsDNA viruses ssDNA viruses
ReverseTranscriptase: dsDNA-RT viruses ssRNA-RT viruses
RNA Viruses: dsRNA viruses
(-)ssRNA viruses (+)ssRNA viruses
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Reports of the International Committee on Taxonomy of Viruses
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感染细菌的病毒
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感染人类和 动物的病毒
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感染植物的
病毒
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感染昆虫的病毒
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Hosts of viral infection
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Structural difference of animal and plant viruses
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Adenovirus
Naked Viruses
Tobacco Mosaic Virus
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Enveloped
viruses
HBV Ebola VirusHIV
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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
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Life Cycle
entry
endosome
secretary vesicle
release
Nucleus
ER
Golgi
coated vesicle
ERGIC
co-translation
N
S
decapsidation
genomic RNA 1a/1b (rdrp)
genomic RNA (RNA1)
subgenomicRNAs
nucleocapsids
(-) strand RNA
HE
translocationM
E
Coronaviruses
② ③
①
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Class I fusion proteins
HA1 HA2Tm+E d
Tm+E dgp120 gp41
S1Tm+E dS2
正粘病
毒
逆转录病
毒
冠状病毒
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)
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Class l Membrane Fusion
flu
HIVRSV
SV5
6-Helix Bundle
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Class II fusion proteinsFlaviviruses: E protein (Dengue, YF, TBE, WN)
Alphaviruses: E1 protein (Sindbis, Semliki Forest)
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Genes and proteins of Flavivirus
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E protein of Flavivirus
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Transformation of E protein
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Class III fusion proteins
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FAST Proteins of Reoviruses (Fusion-associated Small Transmembrane)
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Cartoon show:
Inhibition of membrane fusion : A new target for antiviral therapy
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Membrane fusion
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Fusion inhibition
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Homework-1
Stephen, C. Harrison (2008) : Viral membrane fusion.
Nat. Struct. & Mol. Biol. 15, 690-698
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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
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Cells and viral replication
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Trafficking of cellular and viral Proteins
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Genes and proteins of HIV
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HIV Entry to and release from cells
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MVB and ESCRT
Multivesicular bodies (MVBs) and endosomal sorting complex required for transport (ESCRT)
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Gag and HIV Assembly
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Genes and Proteins of Influenza VirusPB2 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
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Membrane Scission of Influenza Virus
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Homework-2
J.B. Rossman, X. Jing, G.P.Leser and R.A. Lamb
Influenza Virus M2 Protein Mediates ESCRT-Independent
Membrane ScissionCELL 142, 902–913, 2010
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Lipid Rafts
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MA protein interacts with lipids
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Myristoylation of HBV and HDV preS1
H. Yan, et al., (2012) Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife,1:e00049
L M
S
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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, 98-106
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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
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Diversity of Viral Receptors
HSV-1,-2, CMV, Dengue, Sindbis, Vaccinia
HIV1, HHV7
Rhino-
EB
Conona-
Influenza, Reo-, et al.
Polio-
Entero-
Measles
Hepatitis C
CD4
Icam-1
CD21
CD13, ACE2
CD81/LDLR
Sialic acids
Pvr
CD55,Val-2,Vitronectin R
Heparin Sulfate
CD46
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Specificity of Viral receptor
H 高特异性受体CEACAMs (Carcinoembryonic antigen-related cell adhesion molecules): MHVACE2 (Angiotensin-converting enzyme 2 ):SARS-CoV and HCoV-NL63DPP4 (dipeptidyl peptidase 4): HCoV-EMC
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)
M 中等特异性受体APN (Aminopeptidase N):Human APN:HCoV-229EPorcine APN:TGEVCanine APN:CCoVFeline APN:FCoVAlpha-coronavirusesCoronavirus receptor
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HIV Co-receptor: CXCR4 and CCR5
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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 TNF- α/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 IFN- γ/ 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
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Coronavirus and S protein RBD
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8,098 case774 deaths
25 countries
SARS: 2002-2003
http://www.nature.com/nature/focus/sars/map.html
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WHO: Global Alert and Response
Dr. Carlo UrbaniFebruary 2003
Hanoi, Vietnam
2012(5,73)
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SARS Time-Course
The Chinese SARS Molecular Epidemiology Consortium (2004) Science 303,1666-1669
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Molecular evolution of SARS-CoV
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Variation of S protein RBD
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Adaptation of SARS Coronavirus to Humans
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Transmission of Coronaviruses
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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。
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Thank you!