HIV

Question 1

replication cycle of HIV

Answer 1

• First must get in by to cell by binding to specific receptors on cell
  
  • HIV - GP120 recognizes CD4 receptor and binds with high affinity
  • Conformational change occurs, allowing binding of gp120to co-receptor (chemokine receptor) CCR5
  • GP41 exposed, allow Fuse with cell membrane release nuclear capsid
  • RNA genome - first makes a DNA copy of RNA genome , reverse transcription, reverse transcriptase is made by the virus and is carried in
  • PIC = pre-integration complex - carried into nucleus, and integrates by integrase enzyme into the host genome - now called a PROVIRUS
  • Translation occurs:
    ○ Only from an integrated provirus, only when the cell is activated
  • When activated, assembly of viral parts, enzymes etc., budding and release
    Maturation - protease important here for formation of virus, cleaving of functional proteins like GP120

Question 2

why does the immune system fail to control HIV

Answer 2

Early on, massive depletion in CD4 T cells - mostly from intestine, lymphoid tissue and blood - see a loss of lymphoid aggregates and t cell reduction - especially memory

Anti-HIV response from body - results in a small increase, and early control of the virus by the immune system
CD8+ T cell response:
* Recognize endogenous ligands - meaning cells that are infected by a virus and antigen is presented on MHC 1
* Proliferate, and become memory CD8+ or cytotoxic killing cells - cause apoptosis, cell dies that is infected by HIV

However, CD8+ cells fail to full remove ALL HIV from system because:
- HIV mutates to escape the CD8+ cell response of recognizing certain epitopes
* Mutation is rapid, immune system drives the evolution of the virus
* Reverse transcriptase and RNA polymerase 2 lack proof reading ability
* High viral turnover rate
- Also CD4+ cells are helpers for activating CD8+ response
* Enhancing proliferation, differentiation and memory formation
* As CD4+ function is impaired –> CD8+ cell response is not at full potential
- CD4+ cells help B cell response
* B cells without help, cannot proliferate and produce antibodies properly
- HIV is good at neutralizing epitopes
* Makes it hard for cells to recognise, due to sequence variation/mutation, masking and the glycan shield
- Also a cellular reservoir of HIV infection
* Latently infected CD4+ cells - not expressed / translated until activated, but provirus there waiting
* These latently infected CD4+ cells have a long half life - any infection, activate - translation begins

Question 3

HIV –> AIDS

Answer 3

AIDS - acquired immunodeficiency syndrome
- Very low CD4+ T cell count , below 200 cells/mm3
- Opportunistic diseases - patient presents with - can be severe and lead to death
- Increase cancer risk and intracellular infections

Question 4

common HIV caused cancer

Answer 4

kaposi’s sacroma / HHV8

Question 5

• Common viral infection by HIV

Answer 5

• CMV, cytomegalovirus = herpes family

Question 6

other common infections in AIDS

Answer 6

pneumonia common , and mycobacterium tuberculosis
toxoplasmosis