Data produced by the Laboratory of Tumor Cell Biology indicate that human natural killer cells began de novo expression of the helper/inducer phenotype marker CD4 in response to infection by human herpesvirus (HHV)- 6. It was also shown that the CD4 molecules produced in response to the virus could act as competent receptors for the human pathogen human immunodeficiency virus type I (HIV-1), and that productive infection was established in natural killer cells, a cell type normally refractory to HIV-1 infection. Further experiments demonstrated that the receptor for a new human herpesvirus (HHV-7) is also CD4, and that HHV-7 and HIV-1 mutually compete for the same cellular ligand. HIV-1 infection of CD4 lymphocytes is significantly diminished in the presence of HHV-7, and the HIV-1 coat protein blocks HHV-7 infection. Other experiments have shown that HIV-1 infection of peripheral blood lymphocytes results in an increased adherence of the cells to specific extracellular matrix proteins, and that several of these proteins possess the ability to increase the expression of HIV-1 in vitro. Finally, recent results from experiments investigating the pathogenic mechanisms of acquired immunodeficiency syndrome-associated Kaposi's sarcoma (KS) have demonstrated a pivotal role for basic fibroblast growth factor. Related investigations have also shown that the HIV-1 regulatory protein Tat has pleiotropic effects on normal cells associated with the vascular bed, the milieu from which KS arises. Tat was shown to induce morphological changes in normal smooth muscle cells and endothelium which is reminiscent of the spindle cells believed to be the tumor cells in KS. Further, the presence of otherwise substimulatory concentrations of certain inflammatory cytokines significantly enhanced the various activities of Tat, indicating that immune stimulation is probably more significant in KS than immunosuppression.
