HIV pathogenesis

Question 1

What is the global impact of HIV on women?

Answer 1

In Sub-Saharan Africa young women are four times more likely to be infected with HIV than young men highlighting a significant gender disparity.

Question 2

What are the primary subtypes of HIV-1 globally?

Answer 2

HIV-1 consists of many subtypes or clades with subtype C being the most prevalent particularly in Africa.

Question 3

What are the main ways to control HIV-1 infection?

Answer 3

Control methods include antiretroviral therapy post-exposure prophylaxis pre-exposure prophylaxis microbicides and vaccines.

Question 4

What are the two types of HIV-1 vaccines in development?

Answer 4

Vaccines are being developed to prevent HIV-1 transmission prophylactic vaccines and to slow disease progression therapeutic vaccines.

Question 5

What are the key targets for HIV vaccines in the viral lifecycle?

Answer 5

Targets include structural proteins like Gag Pol and Env as well as regulatory proteins like Tat Rev Vif Vpr Vpu and Nef.

Question 6

What is the role of Vif in the HIV lifecycle?

Answer 6

Vif counteracts intracellular retroviral restriction factors like APOBECs allowing the virus to replicate effectively.

Question 7

What is the role of Vpr in the HIV lifecycle?

Answer 7

Vpr enables the reverse-transcribed RNA to localize to the nucleus by providing a nuclear membrane signal.

Question 8

What is the role of Vpu in the HIV lifecycle?

Answer 8

Vpu downregulates CD4 expression at the cell surface limiting superinfection and enhancing virus release.

Question 9

What is the role of Nef in the HIV lifecycle?

Answer 9

Nef downregulates MHC class I and CD4 expression aiding immune evasion and enhancing viral replication.

Question 10

What are the two main areas of focus for HIV vaccine development?

Answer 10

Vaccine efforts focus on antibody responses targeting the Env protein and cellular immune responses involving CD4 and CD8 T cells.

Question 11

How does HIV-1 escape antibody responses?

Answer 11

HIV-1 uses hypervariable regions of the gp120 protein and N-linked glycans to evade neutralizing antibodies and immune detection.

Question 12

What are the functions of the gp120 and gp41 proteins in HIV-1?

Answer 12

Gp120 binds to CD4 and co-receptors for entry while gp41 facilitates membrane fusion enabling the virus to infect the host cell.

Question 13

What are the mechanisms of antibody action against HIV-1?

Answer 13

Antibodies can neutralize the virus opsonize for phagocytosis activate complement or mediate antibody-dependent cellular cytotoxicity.

Question 14

How does HIV-1 use co-receptors for entry?

Answer 14

HIV-1 binds to CD4 and uses co-receptors like CCR5 or CXCR4 for entry which can be blocked by specific antibodies.

Question 15

What is the significance of CCR5 and CXCR4 in HIV infection?

Answer 15

Early HIV-1 strains typically use CCR5 for entry while advanced strains often switch to CXCR4 increasing virulence and progression to AIDS.

Question 16

What is the role of CD4 T cells in HIV-1 immunity?

Answer 16

CD4 T cells help coordinate immune responses by presenting antigens and supporting both B cells and cytotoxic CD8 T cells.

Question 17

How does HIV-1 impair CD4 T cell function?

Answer 17

HIV-1 infection leads to loss of CD4 responses reducing immune coordination and accelerating disease progression.

Question 18

What is the role of CD8 T cells in controlling HIV-1 infection?

Answer 18

CD8 T cells recognize and kill infected cells by releasing perforin and granzymes targeting antigens presented via MHC class I.

Question 19

How does HIV-1 escape cytotoxic T lymphocyte responses?

Answer 19

HIV-1 accumulates escape mutations in epitopes recognized by CD8 T cells reducing the effectiveness of cytotoxic responses.

Question 20

Why is developing an HIV vaccine challenging?

Answer 20

The high mutation rate of HIV-1 results in significant genetic diversity and immune escape making it difficult to create a universally effective vaccine.