HIV/AIDS Flashcards
What kinds of cells does HIV infect?
Memory and activated T-cells, macrophages, microglia, and dendritic cells. Unactivated T-cells and CTLs do not suffer infection.
APOBEC3G
A protective mechanism/active enzyme that NAIVE T-cells have. It introduces mutations into the viral DNA, preventing it from replicating. Unfortunately, activation of a T-cell renders the enzyme inactive, so it can no longer mutate viral DNA; the virus can now infect the activated T-cell.
Vif
HIV’s counter-mechanism to the protective APOBEC3G; it promotes degradation of APOBEC3G by cellular proteases, rendering the T-cell unprotected.
Relationship of NF-kB to HIV virus
Activation of T-cells causes phosphorylation of IkB. IkB releases NF-kB, which then heads to the nucleus to bind to the promoter region of various genes for cytokines expressed in activated T-cells. The long-terminal-repeat sequences that flank the HIV genome also contain NF-kB binding sites that can be triggered.
Viral Vpr Gene
The Vpr protein allows nuclear targeting of the HIV reintegration complex through the nuclear pore, allowing the virus to infect and multiply in terminally differentiated, non-dividing macrophages.
Macrophages and HIV
The virus can replicated inside of the macrophages, but macrophages themselves are pretty resistant to HIV toxicity; therefore, even after T-cells decline, macrophages can continue to be an important site for viral replication. In addition, blood monocytes may be vehicles for HIV to be transported to the nervous system.
What causes brain damage seen in HIV patients?
It is likely the viral products and soluble factors, such as IL-1, TNF, and IL-6 produced by infected microglia. Also gp41 may induce nitric oxide production in infected microglial cells.
Acute (early) infection
1) Infection of memory CD4+ T-cells expressing CCR5 in mucosal lymphoid tissues; no viremia yet
2) Dissemination of virus, in large part due to dendritic cells, who pick up the virus, present it to naive T-cells, and end up infecting said T-cells via direct cell-to-cell contact.
3) Within DAYS, viral replication begins in lymph nodes, which leads to viremia
SUMMARY
- Mucosal infection
- Viral replication occurs within days, leading to viremia
- Viremia leads to infection of helper T-cells, macrophages, and dendritic cells in peripheral lymphoid tissue
- Seroconversion seen within 3-7 weeks of infection, as well as virus-specific CD8+ T-cells; virus titer falls by week 12 as a result
- The viral load at the end of the acute phase reflects the eq’m between the virus and the host response, and may remain stable for several years
Acute Retroviral Syndrome
The clinical presentation of the initial spread of the virus that occurs 3-6 weeks after infection. Symptoms are sore throat, myalgias, fever, weight loss, and fatigue, resembling a flu-like syndrome.
HIV-1 RNA levels
These levels show the extent of viremia; they are a marker of disease progression.
Viral set point
The viral load at the end of the acute phase that represents an eq’m between viral load and host response. It predicts the progression of the disease.
Most reliable short-term indicator of disease progression?
CD4+ T-cell count
Sites of HIV replication during chronic phase?
lymph nodes and spleen; a majority of peripheral blood T-cells do not harbor the virus, but because T-cells are being wiped out in lymph nodes and spleen, the number of circulating T-cells declines.
Chronic Phase
- CD4+ T-cells are at first replaced as quickly as they are destroyed
- However, continuous cycle of virus infection, T-cell death, and new infection leads to a steady decline in the number of T-cells.
- Host defenses begin to wane, and infected T-cell number increases
- HIV RNA levels increase as host begins to lose battle with the virus
- Last 7-10 years in the absence of treatment
Chronic Phase Symptoms
patients are either asymptomatic or develop minor opportunistic infections like oral candidiasis, vaginal candidiasis, mycobacterial tuberculosis, and herpes zoster
