HIV Progression to AIDS: Bioinformatics Approach to Determining the Mechanism of Action

Norbert      Nwankwo; Huseyin      Seker

doi:10.2174/1570162X11311010005

Abstract

The mechanism by which HIV infection transforms into AIDS disease is unclear. Several factors such as the decline in immune response, increase in replication rate, Syncytium inducing capacity and ability of the viruses to infect tumour cell lines are found to be associated with HIV progression to AIDS. What has not been investigated is the role of an increase in affinity for the CD4+ T cells by the HIV-1 T cell lymphocyte-loving (T-tropic) viruses. They are known to be mutants of the Macrophage-loving (M-tropic) viruses and dominate the late stage of the HIV infection in the disease progression.

To elucidate the mechanism by which HIV is transformed into AIDS, this role is examined by using the Resonant Recognition Model (RRM). This is achieved by comparing the degree of affinity between the host CD4 and the gp120 from the HIV-1 M-tropic and HIV-1 T-tropic viruses as well as the isolates of HIV-2 and Simian immunodeficiency virus (SIV).

The results reveal that only HIV-1 T-tropic viruses bind effectively to the CD4 suggesting that T-tropic viruses, which were identified to have mutated from the M-tropic viruses, acquire enhanced and long-lasting attachment to the CD4. This sustained affinity brings about continued attack on the diminishing CD4 until the immune system of the host collapses, which manifests clinically as AIDS. The findings therefore suggest an approach that should target the Variable region 3 (V3) of the HIV-1 gp120 at the early stage of the infection as a part of the HIV/AIDS management procedure. This procedure is essential as early initiation of HIV/AIDS therapy is generally assumed to prevent the spread of the virus and deterioration of the host immunity.

The study is expected to help better understand the HIV pathogenesis and re-strategise pharmaceutical approaches to designing new HIV/AIDS therapeutic interventions.

Keywords: CD4, gp120, Macrophage-loving viruses, Resonant Recognition Model, and T-cell lymphocyte-loving viruses, HIV, CF, immune, V3