Lecture 6 - Viral Entry, attachment and Exit Flashcards
What are the steps in viral replication?
- Virions bind to receptors on host cell surface
- Virion (or viral genome) enters the cell
- Early viral genes are expressed
- Early viral proteins direct replication of viral genomes
- Late mRNAs are made from newly replicated genomes
- Late viral proteins package viral genomes and assemble virions
- Progeny virions are released from the host cell
What is part of the Host Cell Membrane Biology?
- Lipid bilayer with embedded proteins; “fluid” mosaic
- Surrounds cytoplasm of the cell, separating intracellular components from extracellular environment
- Integral membrane proteins span the entire membrane
- Glycoproteins, receptor proteins, channels, and pores
What is Viral Tropism?
Tropism: targets and infects a certain cell type; can be species specific
What is host range?
Host range: different types of cells or organisms a virus can infect
Broad (e.g. rabies)
Narrow (e.g. HIV)
Describe what cell surface receptors are
Attachment proteins on capsid or envelope must bind cell surface receptors
Proteins, glycoproteins, carbohydrate, or lipids
Receptors usually paly roles in normal cellular activities
Efficiency of viral attachment dependent on:
density (cell receptor and viral ligand)
pH, temperature, ions
+/- co-receptor
Describe the attachment of Influenza
Glycoproteins are important intergral membrane proteins. Sialic acid can be found as the last sugar in the glycoprotein chains Influenza hemagglutinin (HA) attaches to sialic acid Sialic acid linkages dictate host range: Alpha (2,3) linkage = Avian influenza virus strains Alpha (2,6) linkage = Human influenza virus strains
Describe the attachment of HIV
Freely diffusing HIV virion “bumps” into host cell (CD4+ T cell)
Viral gp120 specifically binds to CD4
Co-receptor needed for fusion and entry.
gp41 exposed upon gp120 binding to CD4
fusion with host cell
What are Viral Co-receptors?
Some viruses need one receptor for binding and a second receptor for entry (co-receptor)
Example: HIV
HIV Gp120 interacts with CD4 and chemokine receptor CCR5 or CXCR4
What is involved in Viral receptor interference?
ig. what is a superinfection?
Superinfection: a cell previously been infected by one virus gets co-infected with a different strain of the virus, or another virus, at a later point in time
Can lead to reassortment
Some retroviruses (HIV) induce receptor interference
cells infected with one virus remain resistant to superinfection by a virus that uses the same receptor
infected cells remain susceptible to infection by viruses that use different receptor
What are the methods of entry in naked viruses and enveloped viruses?
Naked viruses
Direct penetration (capsid rearrangement)
Receptor-mediated endocytosis
Enveloped viruses
Fusion
Receptor-mediated endocytosis
What is nuclear targeting?
In general, DNA genomes need to end up in the nucleus
Nucleoproteins contains a nuclear localization signal (NLS) to target viral DNA to the cell nucleus
Example: HIV Tat protein
What are Clathrin-coated pits?
Clathrin: protein that forms a triskelion shape; triskelia interact to form a lattice (“cage”) that surrounds a vesicle
Clathrin-coated vesicles sort cargo originating at the cell membrane
Vesicles un-coat and fuse with endosomes (pH 5-6; V-ATPase proton pump)
Endosomes fuse with lysosomes (digestive enzymes; pH 4.5)
What is viral entry with endocytosis?
i.e. define pH dependent
pH dependent: fusion between viral envelope and endocytic membrane occurs only at an acidic pH
release of nucleocapsid into cytoplasm
What is viral release?
Virus may be released by:
Host cell lysis (lytic viruses)
Budding ( if enveloped)
Viruses obtaining their envelope from the cytoplasmic membrane are released during the budding process
What is viral lysis?
Requires that its host cell be destroyed (and virus replication within that host stopped) in order for progeny virions to be released and allowed to disseminate to new cells
Naked viruses are predominately released by host cell lysis.
