HIV Flashcards
HIV belongs to the family of __ that have reverse transcriptase, which does what? What is the consequence of the high error rate of this virus?
HIV belongs to the family of retroviruses that have reverse transcriptase, which converts rna to dna.
high error rate = rapid evolution and drug resistance
There’s 2 types of HIV, ___. Within HIV1, we have groups, M, N, O and P.
Group __ of __ is responsible for the pandemic
There’s 2 types of HIV, 1 and 2. Within HIV1, we have groups, M, N, O and P.
Group M of HIV1 is responsible for the pandemic
Label the component and name the function of the HIV structure
Gag p17: matrix protein – makes the matrix
Gag 24: capsid protein
(something about getting an eating disorder at these ages - get it? gag? eating disorder? …okay)
Label the component and name the function of the HIV structure
Gp41 and GP120: responsible for entry into new target cell
Label the component and name the function of the HIV structure
Integrase
RT (encoded by pol genes - RIP Pol)
Label the component and name the function of the HIV structure
HIV RNA
Protease (encoded by pol)
HIV has different routes of transmission. Name 2
Mucosal and parenteral
1.Mucosal transmission:
Sexual contact (genital and GI tract mucosa) - horizontal
Mother to child: birth canal, breastfeeding - vertical
2.Parenteral transmission:
Vein injection, skin injection, intramuscular injection
Describe the graph below
Left to right in the absence of treatment:
Decrease in CD4 count and increase in HIV rna – HIV targets CD4 T cells, and it replicates in lymphoid tissues. Since CD4 T cells are supposed to mount an immune response against infection, they migrate to lymphoid tissues to inform other cells that an infection is happening (so your overall blood count is going to be low for these two reasons)
In the early stages of infection, the immune system is able to contain the viral infection but not clear it, so it lies dormant. Over time, viral replication slowly continues while CD4 counts slowly drop until you reach an inflection point.
At this point, there is a sharp increase in HIV rna copies and sharp decrease in CD4 T cells. Pt becomes susceptible to opportunistic infections and eventually pt dies
There are 3 phases of untreated HIV infection. Name them.
Acute
Chronic/Latent
AIDS
Describe what happens in each phase of untreated HIV infection
Acute phase: 3 week period. From infection to viral setpoint
Chronic phase: lasts between 3-20+ years
AIDS phase: when opportunistic infections happen and the patient eventually dies
What is the significance of Fiebig Stage 3?
Fiebig stage 3: when patient produces antibodies against HIV (seroconversion) – when pt is considered HIV+
Outline the lifecycle of HIV
(in words)
attachment to receptor (CD4) and co-receptor (CCR5/CXCR4) >> fusion >> reverse transcription + uncoating >> nuclear entry and intergration >> synthesis of viral components >> assembly >> release + maturation
The therapeutic targets for HIV entry include ___ (anchor protein), ___ and ___
GP120 binding to CD4
the Gp120-Cd4 complex binding to CCR5/CXCR4
Gp41 insertion into target cell (fusion)
Which CD4 coreceptor is used by HIV that enters thru mucosal transmission?
Which CD4 coreceptor is used by HIV that enters thru parenteral transmission?
What is a dual tropic virus?
CCR5 – expressed on CD4 cells in the lymphoid tissues; main co-receptor in mucosal transmission
CXCR4 – expressed on CD4 cells in the blood; main co-receptor in parenteral transmission
Dual tropic viruses don’t care about the receptor, they use both
A mutation in which coreceptor may be protective against HIV infection?
CCR5. Apparently homozygous folks are very resistanct to the HIV strains that infect through CCR5 binding.
Reverse transcriptase is an important target for which 3 drugs?
What 2 other HIV enzyme is an important drug target?
Three classes of RT inhibitors:
Nucleoside analogs
Nucleotide analogs
Non-nucleoside analogs
**
Intergrase (integrates viral genome into host machinery)
Protease (facilitates the maturation of assembled virions to become infectious agents)
What are the 3 important structural genes in the HIV genome?
gag - encodes gag p24 and p17
pol - encodes R, I and P (RIP Pol)
env - encodes GP120 and GP41
You just need to see this one
What are the mechanisms of immunodeficiency?
see below
**
Impaired T cell function: due to decrease in CD4 T cells and alteration of cytokine signaling; dysregulation of cytokine production leads to ineffective CD8 T cells
Plasmacytoid dendritic cells produce interferon alpha (necessary for fighting against viral infection), but INF-a is being overproduced which leads to inhibition of T and B cell proliferation so that’s no bueno
HIV infected cells are killed directly via which 2 processes?
Apoptosis
Pryoptosis
What is the difference between apoptosis and pryoptosis?
Apoptosis if you’ll recall is the regular programmed cell death that happens thru caspase 3. This is a NON inflammatory process
Pryoptosis is an inflammatory cell death caused by HIV infection of a quiscent CD4 T cell. It’s an abortive infection that leads to the activation of caspase 1 and release of 1L-1B
What are 3 indirect ways that HIV infected cells are killed?
Antibody dependent cell phagocytosis
Antibody dependent cell cytotoxicity
Cytotoxic T lymphocyte-driven killing via release of perforin and granzyme B
Uninfected cells can also be affected by HIV infection how?
HIV infection causes upregulation of CD95 on bystander cells (uninfected cells). CD95 is recognized by CD95L on an HIV infected cell, activating apoptosis in the bystander cell
GP120 on an infected cell can also bind CXCR4 on an uninfected cell which activates the p53 pathway leading to apoptosis
T/F: We can’t prevent or control HIV infection
Falsehood
Apparently: there’s some sex workers somewhere that have chronic exposure to HIV but don’t get infected, then there’s Elite controllers - control replication and Long term non progressors - have high levels of viremia but CD4 count doesn’t drop
T/F: We don’t have a vaccine for HIV
False.
T cell based vaccine – only works on cells that are already infected so it can act as a therapeutic vaccine (point is to improve CTL killing responses against already-infected cells)
B cell vaccine – acts as a preventative vaccine and aims to generate immunity prior to infection (point is to get antibodies that block infection in the 1st place)
What are the challenges for a B cell based vaccine against HIV?
High diversity of HIV-1: complicates neutralization
HIV-1 mutates rapidly (RT): escapes neutralization
Env variably glycosylated: eludes neutralization
Neutralizing epitopes exposed transiently: flees neutralization
What is the mechanism by which ART addresses HIV infection?
What is the biggest hurdle to curing HIV?
Antiretroviral therapy (ART) suppresses viral replication to levels below the limit of detection (viral replication invariably resumes when treatment in interupted)
Biggest hurdle right now is latency: Latent HIV is refractory to ART drugs (they interfere with replication cycle) and invisible to immune system
What is the difference between a sterilizing and functional HIV cure?
Sterilizing cure: complete absence of HIV sequences in the body
Functional cure: presence of HIV sequences, but absence of viral replication after cessation of therapy
What are the different paths to an HIV cure?
see below
