HIV gene regulation and pathogenesis

Human immunodeficiency virus (HIV) is unique among retroviruses in its genetic complexity. Its genome encodes a number of positive, differential, and negative regulatory genes, whose interplay appears to be directed at maintaining a steady, low-level virus expression. Since clinical progression and CD4 cell depletion in HIV-infected individuals appear to correlate with increase in virus expression, and continuous recruitment of new infected cells, the role for cofactors which enhance HIV production becomes significant in the pathogenesis of AIDS. Many environmental and cellular factors have been found to activate HIV. In particular, some viral agents may interact with HIV in contributing to pathogenesis. The leukemia viruses, HTLV-1 and HTLV-2, and several herpesviruses have been shown to stimulate gene expression from the HIV LTR. In addition, HIV tat gene can also activate a DNA virus (JC virus) which is associated with a neurological disease. Finally, immunosuppression by HIV is likely to reactivate latent herpesvirus infections, thus initiating a vicious cycle for further CD4 cell depletion.