Viral Pathogens

Question 1

Define what a virus is

Answer 1

• pathogen that requires/is adapted to invade living host for survival
• recall Baltimore Classification (1-7)

STRUCTURAL FEATURES:
- Strands: sDNA, dsDNA, sRNA, dsRNA
- segmented, circular, or linear genomes
- complementary base pairing?
- reverse transcriptase?
- 3’-5’ or 5’-3’

Question 2

Compare a virus to bacteria and prions

Answer 2

• Pathogenic prions change structures of cellular proteins and recruit increased production of abnormal proteins.
• Similarly to prions, both viruses and prions are non-living and work by invading host cell machinery.
• pathogenic Bacteria and viruses contain genetic material to integrate into host cel machinery
• Bacteria can reproduce without a host, whilst viruses cannot.

Question 3

Understand how viruses are, in a way, “obligate cellular parasites”

Answer 3

parasitic = using host machinery while harming host
obligate = can’t survive w/out host

Question 4

Define essential features of HIV

Answer 4

OUTER ENVELOPE:
- lipid bilayer
- protruding Env spikes = heterotrimers of SU3TM3)
- Gag protein shells = singular shell
GAG= matrix + capsid + nucleocapsid
-NC coating RNA genome

Question 5

Explain essential features of HIV replication with the cell - from entry to exit from the cell

Answer 5

ENTRY:
1. envelope trimer subunits + glycans = CD4 receptor interactions
- CD4 and chemokine receptor (HR1 + HR2)
- variable loops open conformation to expose transmembrane domains
- co-receptor binding = fusion peptide insertion into lipid membrane
- Env timers form 6-helix bundles

2. Release of nucleoprotein core
   Intracellular trafficking via host microtubule tracks

EXIT:
1. host Tsg101 machinery recruited via (PT(S)AP motif and myrystolation post-modification
- abscission = replicated material forms capsid and forced ejection
- capsid proteins gather at plasma membrane
- escort complex pushes viral genome outwards into extracellular space
- poly protein cut up by cellular enzymes = reorganisation to form capsid structure

Question 6

Understand the function of HIV proteins – how new viruses are made from viral proteins

-(how to hijack a factory to make your products instead?)

Answer 6

3. Integration of viral DNA into host DNA with contortion
   enzyme cuts to ensure repair process with viral DNA
   LEGDEF + IN(integrate protein) + TRN-SR2 = interaction with reverse transcriptase => pre-initiation complex

Question 7

Explain how viral proteins influence the cell to facilitate replication

Answer 7

4. Recruitment of cellular genes which = promotion and enhancement of mRNA transcription proteins (TAR+ Tat)
   eg: Lef, Nf-𝝹𝝺
5. Preferential transcription of viral genome (TAR+ Tat)
   - viral tat produced = RNA binding protein = specific to viral RNA = enhancement of RNA production (+ feedback mechanism)
   - REV protein = promotion of viral RNA nuclear export
   - REV + RRE + NES => interaction w/ Crm1 = interact w/ nuclear pore

Question 8

Provide examples of the involvement of viral infections in cancer and immunodeficiency.

Answer 8

• immunodeficiency allows viruses to escape detection
• set load = minimum amount required to preserve clinical latency to escape detection
  proptosis from non-permissive CD4 cells = indirect T-cell death
• inflammation recruitment allows ubereats delivery of more T-cells for infection by virus
  = colonisation of opportunistic infections (HIV associated pathogens - viral bacterial, fungal or parasitic) => infection only possible to host with immunodeficiency

Question 9

Name some examples of HIV-associated pathogens

Answer 9

• HSV
• KSHV (Kaposi Sarcoma herpesvirus)
  primary infection or reactivation from latency
• latency achieved by virus hiding in PNS cell body
• tuberculosis
• salmonella
• candida
• cryptococcus neoformans
• cryptosporidium
• toxoplasma gondii