WE. LOVE. HIV. Flashcards
What does Rb stand for?
retinoblastoma protein
Draw and label cell proliferation blocking!
Retinoblastoma protein binds cell proliferation factor. This leaves t inactive. Also, the p53 protein (which activates Rb to bond). This means cell proliferation is blocked - NO tumor
Draw and label cell proliferation activation!
Viral proteins (E7 and E6) sequester Rb protein and p53, meaning gene transcription continues as cell proliferation factor remains active! CANCER.
What is p53?
It is a tumor suppressor that regulates the cell cycle
Describe and doodle the retroviral cycle.
Entry into cell and loss of capsid envelope. Then reverse transcriptase makes RNA/DNA double helix THEN DNA/DNA double helix THEN integration into the host genome THEN transcription making lots of RNA copies THEN translation into viral proteins and assembly of many new virions.
What is the HIV 3 stage battle plan headings?
1) recognise and attach to host cell 2) delivery of viral nucleic acid into host 3) mutate and reproduce to survive
Deets about step 1 of the HIV battle plan:
1) recognise and attach to host cell - HIV recognises a receptor on the host cells leading to ineffective immune system and eventual DEATH - hence immunideficiencies and a terminal susceptibility to otherwise compatible diseases.
Deets about step 2 of the HIV battle plan:
2) delivery of viral nucleic acid into host: HIV is a retrovirus, it carries ssRNA and enzymes necessary for production of HIV DNA and incorporati0on into host chromosome
DEETs about step 3 of the HIV battle plan:
3) Mutate and reproduce to survive: mutation rate 65x that of influenza. HIV is a moving target. dies w/host and cannot be transmitted by normal means so must rely on sexual urge to survive!!
Doodle a quick HIV structure poster
go girl g g go go go
What does the variable loop V3 in the HIV gp120 interact with? And what does this interaction follow?
Co-receptor, eg CCR5 on macro/mono and CXCR4 on t-cells eventually. Follows binding to CD4.
What is CD4 in relation to HIV virions?
PRIMARY RECEPTOR - but a co-receptor is also required.
What is CD4 recognised by?
gp120 V1/V2 loop region
What is the change required for variants to recognise CXCR4?
Maybe only 1aa change in gp120 V3 loop region.
Quickly recap the process of cell-mediated adaptive immunity that generally works for the body:
All cells (inc Thelper) have on their surface a number of peptides derived from digestion of proteins in their cytosol. These are bound to class 1 MHC proteins. Cyt Tcells scan the surface of all cells and KILL those that exhibit foreign markers on their MHCs via the recognition of MHC1-peptide complex by tcell receptor and co-receptor CD8. TCR binds to MHC-peptide complex and concommitent binding of CD8 from t cell activates t cell, leading to death of target cell via apoptosis.
Why does the cell mediated adaptive immunity thang not work for HIV infected celles?
Because HIV inhibits expression of MHC1 on the surface of the cells they inhabit, so they are not picked up by cyt t cells!
Why does the innate immune system offer a litte more help than the adaptive for fighting HIV?
Because it recognisesthe LACK of MHC1 on the surface of the cells.
Which cell monitors the amound of MHC1 on the immune cells? And how is that cells activity changed by this?
Natural killer (NK) cells, and their activity is inhibited by high levels of MHC1. They selectively kill cells expressing low levels of MHC1
How does HIV respond to NK cells?
Responds by aquiring mechanisms to inhibit apop.
What are some of the strategies used to combat HIV? 5 of them
Inhibiting integrase, inhibit reverse transtcription or transcriptase, inhibit entry (receptors or gp120/41), inhibit protease or vaccines.
How does the inhibiting protease method work?
HIV protease cleaves multidomain viral proteins into the active subunits. It is a dimer of 99aa, with active aspartates in the binding pockets and a flap which closes on the peptide. DRUGS such as crixivan which mimics peptide substrate bus is uncleavable and nelfanavir which is the most popular.
How does antibodies to HIV protease work?
HIV protease peptide and anti-protease fab fragment
How does inhibition of RT work?
Drugs such as zidovudine which is a nucleoside RT inhibitor, works by being a nuceoside analogue that is modified to be recognised by HIV RT and link into growing DNA but without the OH required for further transcription.
What is the current inhibitor therapy being used?
1+ protease inhibitor (potent but side effects), RT inhibitor with 2 nucleoside inhibitors. combos combat resistance.
