Question

Oligodendrocytes do not have a CD4 receptor, and so are not easily, if at all, infected with HIV. They are, however, easily injured by the inflammatory responses of astrocytes and microglia to HIV infection, as well as by expression of Tat and gp120 by HIV infected cells. Microglia are the main HIV producing cells in the brain; they are infected early and remain productively infected throughout their lifespan. Astrocytes are not as easy to infect as microglia; after a short acute reaction that peaks between 2 and 7 days the infection recedes to low, almost undetectable levels. The infection can be reactivated by cytokines, and therefore astrocytes are often thought of reservoirs in the CNS. All three cell types can be injured by Tat, which is heavily expressed by HIV infected cells, as well as gp120, which can alter glutamate pathway signalling. Inflammatory cytokines can also be neurotoxic, and are expressed by non-infected astrocytes and microglia in response to HIV positive cells. These responses exacerbate and accelerate HIV-associated neurocognitive disorders, and may play a role in the development of HAD and HIVE.

Answer 1

The question relates to the impact of HIV infection on the immune system, particularly focusing on how it affects CD4+ T cells and different brain cells. It discusses the indirect damage to oligodendrocytes, the role of microglia and astrocytes in the CNS in the context of HIV, and the challenge of developing an HIV vaccine due to the rapid mutation rate of the virus.

Step-by-step explanation:

HIV infection poses significant challenges, particularly because it involves the destruction of CD4+ T cells, critical components of the immune system. CD4 serves as a receptor for HIV to enter cells, which then significantly compromises the cellular and the antibody-mediated immune response. Regarding the central nervous system (CNS), while oligodendrocytes lack the CD4 receptor, making them less prone to direct infection by HIV, they can be indirectly damaged. Microglia are the main HIV-producing cells in the brain, becoming infected early and remaining productively infected. In contrast, astrocytes are less susceptible to infection, acting as potential reservoirs for the virus that can be reactivated.

Both oligodendrocytes and astrocytes can be harmed by inflammatory responses elicited by HIV-infected cells and by the viral proteins Tat and gp120. These viral components and inflammatory cytokines can disrupt glutamate pathway signaling and exert neurotoxic effects, contributing to HIV-associated neurocognitive disorders. Antiretroviral drugs that target viral proteins necessary for viral replication have resulted in significantly improved outcomes for HIV-positive individuals. However, developing an effective vaccine remains challenging due to the virus's rapid mutation rate, which enables it to evade the immune system. Scientists are looking for stable parts of the virus that can be targeted by vaccines, but a successful candidate has yet to be realized.