Coinfection of CD4+ T lymphocytes with human immunodeficiency virus type-1 (HIV-1) and human herpesvirus type-6 (HHV-6) or human T lymphotropic virus type-1 resulted in enhanced HIV-1 expression and cytopathology, transactivation of the HIV-1 long terminal repeat (LTR), and in the case of HHV-6, significant upregulation of the receptor for HIV-1. Further, coinfection with HTLV-I and HIV-I generated phenotypically mixed viruses capable of infecting a broader range of human target cells. Similarly, when human immune cells were recovered from athymic mice and infected with HIV-1, phenotypically mixed endogenous murine retroviruses/HIV-1 viruses were detected. These phenotypically mixed species also had an expanded range of host cells. Acquired immunodeficiency syndrome-Kaposi's sarcoma (AIDS-KS) cells were found to constitutively produce large amounts of cytokines. Many of the secreted substances were found to have autocrine effects on the AIDS-KS cells and to exert proliferative effects on normal endothelial cells. The HIV-1 tat protein was shown to stimulate the mitosis of AIDS-KS cells. Culture medium from both HIV-1 acutely infected lymphocytes contained tat which caused an increased proliferation of AIDS-KS cells, as did recombinant tat protein. Additionally, several of the cytokines expressed by activated T-cells induced increased proliferation of the AIDS-KS cells. Macrophages were found to allow HIV-1 LTR-tat transactivation only under certain conditions. Minimally manipulated cells did not support transactivation, although cells isolated by adherence or cells treated with specific cytokines did. Finally, the ability of HIV-1 infected macrophages to produce factors capable of inducing an arthritis was also investigated.
