One of the principal laboratory projects in the Retroviral Diseases Section is the study of HIV replication in M/M. One goal of this effort is to develop anti-retroviral strategies directed at this population. We found that although dideoxynucleosides such as azidothymidine (AZT) are poorly phosphorylated in M/M, they still have potent anti-HIV activity. This is apparently because M/M have low levels of deoxynucleoside-5'- triphosphates. We also observed that certain cytokines, including granulocyte-macrophage colony stimulating factor (GM-CSF) and macrophage colony stimulating factor (M-CSF) can enhance the replication of HIV in M/M, and that these have variable effects on the activity of dideoxynucleosides. We are now investigating the production of cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) by monocytes upon exposure to HIV, and in addition the effect of various cytokines (including IL-10 and IL-12) on HIV replication. We have recently made the observation that IL-10, a cytokine produced by Th2 T cells, is a potent suppressor of HIV replication in M/M. These observations may help explain the pathogenesis of HIV and may provide leads for therapeutic strategies.
