Virus Entry. Steps in virus entry. Penetration through cellular membranes. Intracellular transport John Wiley & Sons, Inc. All rights reserved.

Transcription

1 Virus Entry Steps in virus entry Penetration through cellular membranes Intracellular transport

2 Steps in virus entry How do virions get into cells? Viruses of bacteria, archaea, algae and plants use different entry mechanisms than animal viruses Bacteriophages may puncture through cell wall Plant viruses may enter through mechanical means then spread through plasmodesmata 2011 John Wiley & Sons, Inc.

3 Steps in virus entry Enveloped and nonenveloped viruses have distinct penetration strategies Enveloped viruses can enter by: Fusion and fission of the envelope with the plasma membrane Receptor-mediated endocytosis followed by fusion/fission with an endosome

4 Entry of enveloped viruses Steps in virus entry

5 Steps in virus entry Nonenveloped viruses can enter by: Receptor-mediated endocytosis Passage of genome through a channel in the membrane Some viruses can pass directly from cell to cell Virus passed to neighboring cell by filopodia Virus assembled and transmitted at virological synapse Formation of syncytia

6 Steps in virus entry A variety of cell surface proteins can serve as specific virus receptors or attachment factors

7 Steps in virus entry Receptors interact with viral glycoproteins, surface protrusions, or canyons Many viruses enter the cell via receptormediated endocytosis May occur at clathrin-coated pits, caveolae or lipid rafts Virus then delivered to early endosomes Some viruses enter by macropinocytosis

8 Penetration through cellular membranes Passage from endosomes to the cytosol is often triggered by a low ph Induces conformational changes in virus

9 Penetration through cellular membranes Membrane fusion is mediated by specific viral fusion proteins Generally type I transmembrane proteins that contain fusion peptides Class I fusion proteins Class II fusion proteins

10 Penetration through cellular membranes Fusion proteins undergo major conformational changes that lead to fusion Activated by low ph or receptor binding

11 Penetration through cellular Nonenveloped viruses penetrate by membrane lysis or pore formation membranes Genomes may pass through pores formed by virus Some viruses rupture endosomal membrane

12 Intracellular transport Virions and capsids are transported within the cell in vesicles or on microtubules Dyenin and dynactin move viruses along microtubules

13 Intracellular transport Import of viral genomes into the nucleus Interaction with importins, karyopherins Dissociation of the nuclear membrane during mitosis Import after disassembly at the nuclear pore Transport of intact virions through the nuclear port

14 Intracellular transport

15 Intracellular transport The many ways in which viral genomes are uncoated and released May occur simultaneously with entry May occur after a complex serious of fusion and transport steps

16 How can virus entry be Intercept virus before it reaches cell with neutralizing antibodies prevented? Flood extracellular space with soluble receptor Block cellular receptor Lysosomotropic agents, carboxylic ionophores and bafilomycin A1 inhibit acidification of endosome Inhibit membrane fusion Inhibit uncoating (amantadine, WIN compounds)

17 Fundamental concepts Viral proteins bind to specific receptors on cellular surface Entry may occur by fusion, endocytosis or passage of viral genome through a pore Fusion may be mediated by low ph Nucelocapsids can be transported on microtubules Uncoating of genomes can occur by a variety of means

18 Key Terms Amantadine Bafilomycin A1 Budding Carboxylic ionophors Caveolae Caveolin cavin Class I fusion proteins Class II fusion proteins Clathrin-Coated pits Coiled-coil Cytosol Dynactin Dynein Early endosome Endosome Fission (Membrane) Fusion (Membrane) Fusion peptide Glycolipid Glycoprotein Hemifusion Immunoglobulin family Importin Integrins Karyopherin

19 Key terms Ligand Lipid raft Lysosome Lysosomotropic agent Neuraminidase Plasmodesmata Proteoglycan Receptor Receptor-mediated endocytosis Sialic acid Syncytium (plural: synctia) Type I transmembrane protein Vesicle transport Virological synapse