New insight into HIV/AIDS

A paper published in the March 2011 print edition of the Journal of Clinical Investigation offers new insight into what prompts immunity to AIDS in sooty mangabeys, a natural host African monkey species. According to Don Sodora, Ph.D., a principal investigator in Seattle BioMed's HIV/AIDS research program, "SIV-infected sooty mangabeys use immunologic strategies to prevent the onset of clinical AIDS in the face of high levels of viral replication." He believes that understanding these immunologic strategies will be useful for identifying new approaches to inhibit AIDS progression in HIV-infected patients.

In an HIV-infected person, CD4+ T-cells (white blood cells that play a central role in creating immunity) decline, leaving them vulnerable to other infections and the onset of AIDS. This dramatic loss of CD4+ T-cells is considered to be a key predictive parameter of AIDS onset. However, in sooty mangabeys, simian immunodeficiency virus (SIV)-induced CD4+ T-cell depletion can be comparable in magnitude to that in humans, but the monkeys do not show clinical signs of AIDS. "These studies indicate that SIV-infected sooty mangabeys do not rely entirely on CD4+ T cells to maintain immunity," stated Kiran Mir, Ph.D., of Seattle BioMed, a co-first author of the paper.

The paper goes on to identify an immune cell subset that has the potential to function as CD4+ T cells, but unlike CD4+ T cells, they are resistant to SIV/HIV infection. Termed "double-negative T cells," these immune cells do not express the CD4 protein that is required for SIV/HIV entry and are abundant in sooty mangabeys. According to Sodora, "Double-negative T cells are also present at low levels in humans, and therefore could potentially be able to compensate for the loss of CD4+ T cells in humans as well".

While it is clear that HIV infection in humans is the trigger that leads to CD4 depletion and clinical AIDS, this direct association was not observed in the cohort of SIV-infected sooty mangabeys studied by Sodora and colleagues. This study demonstrates the complexity of the SIV/HIV infection and offers insights into how to use immunologic approaches to potentially help HIV infected patients live longer, healthier lives.