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Define a lentivirus.
Give an example of one.
- A retrovirus (RNA virus) that produces a chronic infection
- with slowly progressive symptoms. It
- does not show true latency in the body but can be non-replicating in some
- cells. Example: Human Immunodeficiency.
Name the two major families of HIV. Which family shows selectivity of
nonnucleoside RT inhibitors?
HIV-1 & HIV-2; HIV-1
Of the HIV-1 subtypes, which group is the most common?
Group M (Others discussed are Group N, Group O and Group P)
In the HIV structure, each viral particle has _____ copies
of the genome surrounded by a ________ which is surrounded by a lipid envelope.
How is the outer lipid bilayer of the HIV structure
Obtained from the host cell when budding
The lipid envelope is studded with viral envelope protein or
_____ that is required for cell binding and uptake into a new host cell.
Name the two proteins gp160 is made of.
Gp120 & gp41
When HIV gets into the cell it already has _________
___________ (2) attached to its RNA.
The small RNA genome encodes for a minimal number of
proteins through several open reading frames.
Name them and what they do.
- Gag: encodes a polyprotein that
- is processed to several viral structural proteins
- Pol: overlaps w/ the gag ORF and
- encodes 3 enzyme activities
- Env: encodes the gp160 protein
Small regulatory proteins
Name the Pol
RNA-dependent DNA polymerase (reverse transcriptase): also possesses RNase activity
- Protease: required for
- processing the larger protein into the functional proteins
- Integrase: required for
- integration of viral-derived DNA into host cell genome
Name the two actions of regulatory
proteins in HIV.
- 1. Enhance
- virion production 2. Inhibit host cell anti-viral mechanism
List the small genes coding for
regulatory proteins in the HIV genome.
- Rev, Nef(activates T cells, enhances ability of the virus to replicate), Vpr
Viral entry into a cell is mediated
by _____ binding to a _______ receptor and the co-receptor __________ present
on lymphocytes or macrophages.
Gp160; CD; CCR5 chemokine receptor
With advancing disease, there is a
shift in co-receptor to the ___________ which allows for CD4+ T-cell uptake.
Once the virus binds to a CD4+
cell, the ______ _______ (2) controls cell membrane fusion.
True/False. Following fusion, the full-length RNA genome
enters the nucleus and is replicated into a RNA-DNA duplex.
False; enters the cytosol
What is the duplexed RNA degraded
by and what happens once it is degraded?
- RNaseH; the 2nd DNA
- strand is copied
About how many transcription errors
are made per RNA genome and what is this resulting from?
- 3; the error-prone nature of the
- HIV RT (this allows for evolution of the organism; too many mutations leads to
- viral death)
After the DNA enters the nucleus,
what is it randomly integrated into the host DNA by?
Which of the following proteins is
not encoded by the HIV pol gene? Regulator of virion, integrase, protease,
Regulator of virion
True/False The integrated DNA is
always immediately used to start virion production.
False; it can remain quiescent
Upon activation, viral proteins
& RNA are synthesized by the host ________/___________ apparatus and new
RNA genomes enclosed in ________________ are produced.
Which proteins concentrate in the
host cell membrane lipid rafts where nucleocapsids are sent and are engulfed?
The initially infected CD4+ cells
generate a strong burst of new HIV particles within ___________ .
About how many cells are initially
infected upon sexual transfer of a few viral particles and what happens to CD4+
- About 109 cell infected;
- levels of CD4+ T-cells transiently fall
During the initial infection, the
viral load (plasma HIV RNA level) falls to a quasi-steady state which reflects
what? (2 things)
- Immune control & HIV
- replication and infection
How often do the infected T-cells
turn over during the initial infection?
Every 2.2 days
With time, the CD4+ T-cell
population becomes exhausted and blood levels start to _________ while viral load
At what level (cells/mm3)
will significant opportunistic infections will occur?
What is the time frame between
initial infection to late stage?
8 to 10 years
What are “long-term
- A subpopulation that can be
- infected for 10-20 years without having clinically significant
- immunosuppression (1 in 500 infected people, have mutations in co-receptors)
Name some HIV Drug Targets.
- Initial entry phase, replication of
- viral genome, processing of proteins, release of mature particles.
Name the 1st successful
Name the classes of antiretroviral
agents for HIV.
- Nucleoside reverse transcriptase
- inhibitors, Nonnucleoside RT inhibitors, HIV protease inhibitors and fusion inhibitors
_________ _________ (4) rely on the host cell to phosphorylate the analog to
generally the triphosphate state.
- Nucleoside/tide Reverse
- Transcriptase Inhibitors
Nucleoside/tide RT Inhibitors block
synthesis by: (2 ways)
- 1. Competitive
- inhibition of nucleotides into growing DNA chain. 2. If incorporated stop chain
- elongation due to lack of 3’-OH group.
All nucleoside/tide RT inhibitors
require triphosphorylation, except for _______ which is a ___________.
True/False. All nucleoside/tide RT inhibitors work
against both HIV-1 and HIV-2 viruses.
Nucleoside/tide RT inhibitors have
_________ __________ (2) for viral DNA polymerase versus eukaryotic DNA
Why is there some mitochondrial
toxicity with nucleoside/tide RT inhibitors?
- They have some activity against
- human DNA polymerase γ
Name the major nucleoside/tide
analog drugs according to their purine/pyrimidine.
Thymidine: Zidovudine (ZDV (AZT)), Stavudine (d4T)
Guanosine: Abacavir (ABC)
Adenosine: Didanosine (ddI), Tanofovir
Name the three kinases that
typically do the phosphorylation events.
- Thymidylate kinase, CMP kinase and
- AMP kinase
For a high level of resistance to
occur with nucleoside/tide RT inhibitors, at least _____ __ ____ _______ ______
3 to 4 codon variations.
As monotherapy agents,
nucleoside/tide RT inhibitors will only reduce the viral load by ____ __ __
percent; however, _______ can lower viral load by 99%.
30 to 90; abacavir