HIV Pathogenesis

Question 1

gp120

Answer 1

One of the proteins HIV uses to enter cells; HIV binds CD4, inducing conformational change that allows subsequent binding of gp120 to CCR5 or CXCR4. This induces conformational change in gp41.

Question 2

gp41

Answer 2

One of the proteins HIV uses to enter cells; conformational change in gp41 allows it to bind the fusion receptor and facilitate entry of HIV into cell

Question 3

Tat & Nef

Answer 3

HIV regulatory proteins. Suppress MHC class I protein synthesis thus decreasing cytotoxic T cell response to infected cells. Also regulates viral transcription

Question 4

Delta 32 mutation

Answer 4

Causes truncated CCR5 that cannot be expressed on cell surface thus giving homozygotes resistance to HIV. Rare, most common among Scandinavian ancestry. Heterozygotes are susceptible but have slower disease progression.

Hypothesized to provide protection against plagues of viral hemorrhagic fevers.

Question 5

Elite controllers

Answer 5

Some patients are inherently resistant to HIV for an unknown reason. Their CD4 levels never go below 500 and HIV RNA is always less than 500 in absence of treatment.
Treatment may not be worth it.

Question 6

acute HIV infection

Answer 6

50-70% are symptomatic seroconverters - high viral load occurs at seroconversion around 3 weeks after exposure.

Question 7

acute HIV infection clinical presentation

Answer 7

general: fever, sore throat, lymphadenopathy, arthralgia, myalgia, fatigue, malaise, anorexia/wt loss

CNS: headache, meningitis, neuropathy, radiculopathy, GB, cognitive impairment

Question 8

asymptomatic phase

Answer 8

specific immune response mounted in a few weeks, viral load decreases from high titer at 3 weeks and CD4 T cell count is near normal levels. HIV viral load steadily increases and CD4 count decreases throughout this phase

Question 9

importance of GALT in HIV infection

Answer 9

GALT is the largest area of lymphoid tissue and is a major site of HIV viral replication and depletion of CD4 t cells, especially in primary infection. Loss of gut barrier leads to bacterial products crossing the gut membrane causing generalized activation of the immune system.

Question 10

how long after exposure does HIV spread throughout the body?

Answer 10

in a matter of days

Question 11

CCR5

Answer 11

found on memory T cells, monocytes and DCs

Question 12

CXCR4

Answer 12

found on memory and naive T cells, monocytes, B cells