FUNCTIONAL ANALYSIS OF HUMAN RETROVIRAL GENES

The primary focus of this project over the last year has been the study of the regulation of the expression of the Human Immunodeficiency Virus (HIV). The goal of the project is the elucidation of the viral and cellular factors that may regulate the activation of HIV expression thus contributing to the pathogenesis of AIDS. Our studies of the regulation of HIV expression have focused on the following systems: (1) we have studied DNA sequences within the HIV LTR that respond to the viral transactivation gene, tat and have identified a four-base pair segment crucial for tat activity; and (2) we have analyzed the activation of HIV expression in promocytic cells constitutively producing low levels of HIV and have shown that lymphokines and monokines can induce high levels of HIV expression in these cells. An additional series of studies has addressed the problem of transplacental infection by HIV. We have demonstrated that the human placenta contains CD4 mRNA and protein. Furthermore, we have productively infected a human choriocarcinoma cell line with HIV. These studies suggest that prenatal transmission of HIV may occur through infection of placental tissue.