MICB 212 Viral Replication Infectious Cycle (General)

viral tropism

virus must find the right cell

high specificity when binding to cell receptors

specific surface (spike/capsid) proteins that recognize and bind to receptor molecules on host cell membrane

only cells with matching receptor can be infected by virus

viral infectious cycle (basic)

1. binding to cell receptor

2. entry & uncoating

3. early gene expression

4. replication of viral genome

5. late gene expression

6. assembly of virions

7. exit

binding to cell receptor

viruses recognize and bind to specific receptors of cells they infect (host specificity)

virus encoded proteins bind to specific proteins, carbohydrates or lipids on the cell surface

entry and uncoating

virus enters cell after attachment and passes through cell wall/membrane

capsid disintegrates to release genome (uncoating)

how do virus pass through cell membrane/wall in the viral cycle

bacteriophages inject their genome directly into cells

enveloped viruses fuse with cell membrane

plant viruses penetrate cell wall but damage it because there’s no receptor viruses can bind to

non-enveloped viruses enter via endocytosis

early gene expression

viral genome directs expression of early proteins

molecular pathway to produce viral mRNA

replication of viral genome

early proteins promote replication of viral genome

DNA viruses use host nucleus

RNA viruses replicate in the cytoplasm

late gene expression

viruses express late mRNA from newly replicated genomes

late viral proteins are structural proteins used to make viral particles

assembly of virions

structural proteins package new viral genomes and assemble capsid

enveloped viruses encode glycoproteins that are inserted into lipid membranes and direct formation of viral envelope upon release

exit

viruses leave host cell to find and infect new host cells to re-initiate replication cycle

progeny virions released from host cell

lytic viruses burst host cell, killing it

enveloped viruses bud off from membrane taking part of it as their envelope

viral propagation

process where viruses infect a host cell, use cell to replicate and spread to new cells or hosts

viral propagation few cells infected

infect a few cells at the same time → eclipse period where viruses making and assembling viral particles → release some viral progeny cells → those viral progeny cells make make and assemble more viral particles → second release of viral progeny cells

viral propagation all cells infected

infect all cells at the same time → eclipse period where viruses are making and assembling viral particles → release all viral progeny at the same time

viral receptors

different viruses can have the same receptor

viruses in same family may bind different receptors

one virus may bind multiple receptors

virus may use different receptors on difference cell types

enveloped virus binding

bind via transmembrane glycoproteins

enveloped replication

viral entry: penetration + uncoating at plasma membrane

enveloped viruses bind to specific receptors on host cell membrane

virus envelope fuses directly with host cell membrane

triggered by receptor binding or change in temperature/pH

enveloped replication

viral entry: fusion at plasma membrane

enveloped viruses bind to specific receptors on host cell membrane

binding causes conformational change in viral fusion proteins → activates fusion machinery → viral envelope and host cell membrane merge → fusion pore opens → genome released

enveloped replication

viral entry: viral fusion with endosomal membrane

enveloped viruses bind to specific receptors on host cell membrane

virus engulfed by cell and taken into endosome

endosome becomes acidic after maturation → conformational change in viral fusion proteins → viral envelope fuses with endosomal membrane → fusion pore opens → genome released

enveloped replication

unusual viral entry: endosome fusion receptor

virus doesn’t have receptor on surface of cell

entry via endocytosis/pinocytosis

non-enveloped virus binding

bind via capsid surface or protrusions

non-enveloped replication

viral entry: receptor-mediated endocytosis + pore formation

can’t undergo membrane fusion

virus binds to specific receptor on host cell membrane

cell engulfs virus via endocytosis to form endosome → low pH triggers conformational change in capsid → virus forms pore in endosomal membrane → genome released

non-enveloped replication

viral entry: endosomal escape by lysis or disassembly

can’t undergo membrane fusion

virus binds to specific receptor on host cell membrane

cell engulfs via endocytosis to form endosome → low pH triggers breakdown of endosome/capsid → genome released

viral entry into nucleus

entry via nuclear pore complex with NLS

entry during cell division when nuclear membrane breaks down