Virus Replication

Virus Replication

1. 1. ENTRY

   • Receptors
     • abundant
       • Influenza - sialic acid oligosaccharides
     • Specific
       • Rabies - nicotinic acetylcoline
     • sometimes primary (CD4) + secondary (CCR5/CXCR4)
   • Metastability
     • being in an unstable + transient, but long-lived state 
     • receptors = catalyst
     • energy spring-loaded in assembly -> potential energy to disassemble
     • precursor state -- (maturational cleavage) --> metastability -- (receptor binding, entry) --> stable state
   • Strategies
     • fusing 2 membranes
     • Enveloped
       • e.g. influenzae heamagglutanin
       • trimer - 3 identical monomers - each do this
         • HA0 --(cleaved)--> HA1 + HA2
           • new N + C terminus. Increased free energy.
             • N terminus hydrophobic (fusion peptide) -> inserts into target membrane
               • Bind to sialic acid receptor -> endocytosis
                 • low luminal 5.5 pH -> conformational change
                   • trimeric structure bends -> pulls membranes together -> FUSION
                     • virus released to cytoplasm near nucleus
     • Non-enveloped
       • e.g. Polio
       • Bind to membrane -> icosahedron proteins move relative to each other
         • hydrophobic VP1 helix revealed
           • sticks to membrane -> forms pore
   • Uncoating
     • Enveloped
       • direct fusion with membrane
         • HIV
       • endocytosis -> endosome acidifies -> fusion -> release
         • I. heamagglutanin
     • Non-enveloped
       • pore formed -> release nucleocapsid to cytosol
         • Polio
       • endocytosis -> release reduced nucleocapsid -> docks nuclear pore -> release to nucleus
         • Adenovirus

2. 2. POST-ENTRY

   • Microtubule-dependent trafficking
     • e.g. Herpes virus

3. 3. GENE EXPRESSION

   • Trancription
     • +ive sense ssRNA
       • used as mRNA
         • direct association with ribsomes in cytoplasm
       • group IV
     • ds + ssDNA
       • host RNA polymerase transcribes directly
       • group I + II
         • enters nucleus -> use host Pol to replicate -> host transcriptase for transcription -> early + late mRNA
     • dsRNA
       • -ive strand transcribed by viral RNA-dep RNApol-> +ive strand used as mRNA
       • group III
     • -ive sense ssRNA
       • group V
     • retrovirus (+ive ssRNA)
       • viral reverse transcriptase forms -ive strand to form DNA-> dsDNA enters nucleus -> integrates into host genome -> transcribed by host pol into mRNA
       • group VI
   • Genome packaging
     • +ive sense
       • viral pol -> -ive strand -> more +ive strands
     • -ive sense
       • viral pol -> +ive strands -> more -ive strands
     • dsRNA
       • +ive strands produced (template) -> -ive strand -> restore ds

4. 4. GENOME REPLICATION

   • Linear DNA
     • Protein priming
       • e.g. Adenovirus
     • Self-priming
       • e.g. Parvovirus
   • Circular DNA
     • Bidirectional origin dependent
       • SV40
     • Rolling circle
       • Herpesvirus

5. 5. ASSEMBLY & EGRESS

   • association of replicated nucleic acid with synthesised capsomeres -> nucleocapsid
   • Enveloped
     • envelope proteins + glycoproteins insert into portions of host cell membrane
       • nucleocapsids associate with these parts (bind to glycoproteins)
         • bud through it
           • envelope = host cell membrane + viral molecules
             • proteases (host enzymes) cleave initial large envelope proteins -> infectious