03-病毒学virus巴斯德研究所.ppt

Virus Entry and UncoatingPaul ZhouInstitut Pasteur of Shanghai General consideration Enveloped viruses – nucleus Enveloped viruses – cytosol Non-enveloped viruses – nucleus Non-enveloped viruses - cytosol General methods to identify receptors and co-receptors for viral entry Permissible and non-permissible cells Non-permissible cells that block early stage of viral replication Indicator cells such as Magi Cell-cell fusion assay Pseudotypes Genetic approaches – animal cross; somatic cell hybrids; transfectants (genomic DNA or cDNA library) Receptor-interference approaches – different viruses; different serotypes; receptor down-regulation; soluble viral attachment proteins; specific monoclonal antibodies Carbohydrate-destroying enzyme – neuraminidase; heparinase and heparitinase; antibodies against galactosyl ceramide Additional complications for viral entry Attachment molecules that capture and transfer virus to target cells such as DC-SIGN Additional proteolytic process Antibody-dependent enhancement of viral entry Receptor-mediated endocytosis and receptor-associated signal transduction Antibody-dependent enhancement of viral entry Dengue virus, West Nile virus, influenza A virus, HIV-1, HIV-2 and EBV Through Fc receptor Alter cell tropism Can occur in mucosal surface through polymeric IgA In suboptimal doses of antibody concentration Receptor-mediated endocytosis in viral entry pH-dependent and independent – carboxylic ionophores and bafilomycin A1 Clathrin-dependent and independent – dominant negative mutants of cellular guanosine triphosphatase (GTPase) dynamin and caveoline Clathrin-dependent: Semliki Forest virus, Sindbis virus, Influenza virus, rhinovirus 14 and adnoviruses Clathrin-independent: poliovirus and MMLV Caveolae-dependent: SV40 pH-dependent pH-independent__________________________Influenza A virus RetrovirusesReoviruses Herpes Simplex Adnoviruses virusesSemliki Forest virus Vaccinia virusVesicular Stomatitis Rotavirusesvi