Lecture 13 Flashcards
There is a decline in infection from 2001 as a result of
anti-retroviral therapy - reduces infectiveness
Circumcision protects men from HIV by about __%
70%
HIV is part of the retroviral family of _________
Lentiviridae, meaning they cause infection slowly
SIV is
did HIV arise from it?
Simmian Immunodeficiency virus
HIV arise from these monkey viruses
The slaughtering of monkeys in africa likely lead to the ______ of HIV variants into humans in the 1930s
Zoonoses
SIV, HIV1/2 all have regulatory proteins __, __, ___
But differ in the variable regions of regulatory proteins
SIV, HIV1/2 all have regulatory proteins gag, pol, env
But differ in the variable regulatory proteins
There are _ single strands of RNA in the HIV virus
2
Env = gp 120 and …
gp120 (Surface; cell attachments) and
gp 41 (Transmembrane fusion domain)
gag consists of
structural proteins
- p17 (MA - Matrix)
- p24 (CA-capsid)
- p7 (Nucleocapsid)
pol consists of
p66/51 (RT-reverse transcriptase)
p32(IN- integrase)
p11 (PR - protease)
clades are seperated by their…
genetic diversity
HIV -1 M groups sits close to….
SIV CPZ
gp120 binds to ____
CD4
Once it binds, the envelope undergoes a conformational changes and binds a second time to _____ and _____
Once it binds, the envelope undergoes a conformational changes and binds a second time to CCR5 or CXCR4 co receptors
Upon entering the cell, the RNA undergoes _____ _______
reverse transcription
makes pro-viral DNA and integrates to the host DNA
what are the key features for HIV replication?
Rapid
Error prone reverse transcriptase leads to rapid evolution of multiple quasispecies
10 billion particules produced per day
If Virus enters an activated CD4+ cell - it is..
If resting…
killed
If resting - latency
True or False
HIV can only affect Cd4+ T cells
False
Can also infect Monocyte/macrophages
Viruses that use CCR5 are called
R5 viruses (95%)
Viruses that use CXCR4are called
X4 viruses
R5 viruses cause ___ T-cell destruction
less
50% of patients with AIDS carry an __ virus
X4 virus (develops later on)
If you are homozygous for CCR5, you are only exposed to rare infection with ___
X4
True or False
CCR5 is not neccessary for immune function
True
True or false
HIV can enter Dendritic, Thymocytes and CD34+ progenitor cells
true
What is the normal role of APOBEC3G?
Which HIV protein blocks it?
Sees foreign RNA and edits so it doesn’t persist in the cell.
Blocked by vif (HIV protein)
What is the normal role of Trim 5 alpha?
Which HIV protein blocks it?
Blocks uncoating of retroviruses
Blocked by capsid
What is the normal role of Tetherin?
Which HIV protein blocks it?
Blocks release of virus
blocked by vpu
What is the normal role of LEDGF?
Which HIV protein facilitates integration?
Tethes HIV to host chromatic
Integrated by Integrase
How does HIV evade the immune response?
Sequence variation - Lack of recognition
Altered antigen presentation - down regulation of MHC class I molecules by Tat, Vpu and Nef
Loss of effector cells - Clonal exhaustion, loss of CD4 Tcell help, Replicative senescence
Latency - silent, evades response
Priveleged sites of viral replication - BB barrier etc…
