Molecular Virology Flashcards
What does AIDS stand for?
Acquired immunodeficiency syndrome
What cell does HIV infect
CD4+
T-lymphocytes, monocytes, macrophages, dendritic cells
How can AIDS be defined
The progressive qualitative and quantitative decline in the CD4+ Th1 lymphocyte subset
Estimated cumulative number of deaths due to HIV
30 million
Where is HIV mainly pandemic?
Sub-Saharan Africa
When was the peak of the number of people newly infected and where are we at today
1997
New infections have reduced by 27%
What is the target of the organisation called UNIAIDS
To reach 0 new cases by December 2015
When was HIV first identified?
1980
When was first isolated?
1983
What was the first discovered HUMAN retro virus?
HTLV-1 in the late 1970’s
What was HIV first called?
LAV/HTLV-3
It was also found to not be closely related to HTLV-1
When was HIV’s genome completely sequenced
1985
What SIV virus was HIV-2 found to be closely related too?
SIVsm
Name the 4 HIV-1 virus groups
M, N, O, P
HIV-1 Group M
M = main group
Responsible for 98% of infect patients
A diverse group with sub types A-K
Where is the epicentre of diversity of the HIV-1 virus
Cameroon
What does HIV-1 O group stand for
Outlier
HIV-1 groups N and O most closely related virus?
SIVcpzPtt
HIV-1 group P most closely related virus?
SIVgor
SIVcpz is a recombinant virus of which two viruses?
SIVrcm and SIVgsn
How is it believed HIV-1 was transmitted to humans?
SIVcpz virus
Bushmeat trade
What 3 causes are believed to be responsible for HIV-1 rapid spread within the population
Intravenous drug use
Blood transfusion
International travel
How is HIV transmitted to other people?
Contact with blood or mucous membrane
Eg sex, blood transfusion
What is transmission rate of HIV via sexual contact?
1-1000 per sexual partners
Why is the transmission of HIV very inefficient?
Mucosal layer provides physical barrier and is the front line innate immune response
Also due to limited target cell availability
Does HIV infection occur from a founder virus?
Yes, and there is strong evidence to support this
What are the risk factors for sexual transmission of HIV-1
High virus load
Presence of cuts, abrasions, irritation, inflammation
Other STD (herpes, syphilis)
Lack of or failure of condom
Mother to child transmission
Accounts for greater than 90% of infant/child infections.
Can be as high as 50% of births to HIV positive mothers
Highest risk during delivery but breast feeding is also significant route of infection
Application of antiretroviral therapy and avoidance of breast feeding. How does affect transmission
Reduces rates of transmission to 2%
HIV home test kits?
Rely on the innate immune response, as they detect antibodies
Provide fast results 20 mins
99% accurate
If a HIV kit test is positive how is this followed up?
A lab test: ELSIA, westernblot
Then use RT-PCR to confirm isolate and look for drug resistance. So optimal treatment can be given
What is the length of HIV-1 genome?
9.3 Kb
HIV-1 genome is flanked by what at each side of the genome?
LTR
These act both as promotors and poly A signals
Name all the genes in HIV-1 genome
Gag Pol Env Vif Vpr Vpu Nef Tat x2 Rev x2
What genes does murine leukaemia virus contain?
Gag, pol and env
What is the structure of the CD4+ receptor?
4 Extracellular IgG like domain and a cytoplasmic tail
What us the structure of the secondary receptors (CCR5 CxCR4).
7 transmembrane helices, virus interacts with the N terminus of the protein
Is integrase a tetramer or a dimer?
Tetramer
Tat
86-101 amino acid
A nucleolar protein
Tat functions
RNA binding protein-transcriptional activator
Activation of quiescent T cells
Induction of apoptosis
What is the name of the stem loop at the beginning of the HIV genome?
TAR RNA
Molecular basis of Tat
Tat recruits host proteins such as cyclin T1 and cdk9
This phosphorylates the RNA pol
Phosphorylation of C-terminus tail of RNA pol II allows elongation.
Where does the RNA pol II bind
TATAA box
What is the function of Rev?
Controls the translation of viral mRNA and movement form the nucleus to the cytoplasm
What sequence does Rev bind and where is this sequence in the HIV genome?
RRE sequence
Found in the envelope protein reading frame
What spliced transcripts is the RRE sequence found in?
Full length and single spliced
NOT multiply spliced transcripts
What does RRE stand for
Rev responsive element
Structure of the RRE?
351bp hilly structured RNA
Name HIV-1 accessory protein (non essential)
Vif, Vpr, Vpu and Nef
What accessory protein does HIV-2 have that is not present in HIV-1
Vpx
Roles of Vif, Vpu and Vpx?
Key roles in counteracting the innate anti-viral response
Role of Vpr?
Induces G2 cell cycle arrest
What technique is often used to study the functions of genes
Reverse genetics
How is Nef stabilised in the PM?
Nef has a myristoylated end that anchors the protein into the plasma membrane
Main roles of Nef
Down modulation of cell surface glycoproteins eg CD4, MHC class I
Enhancement of viral infectivity
Perturbation of cell signalling
Why is down modulation by HIV Nef important?
Prevent sequestration of virus on cell surface
Prevent incorporation of CD4 into new virion envelopes
IL16 signalling via CD4 inhibits LTR activity so is blocked
Block to lethal superinfection
