We are pursuing several broad areas relating to pathogenic human viruses, principally the T-lymphotropic retroviruses and a new DNA herpesvirus, human B lymphotropic virus (HBLV). There are two distinct subgroups of human T-lymphotropic retroviruses: the leukemia viruses, human T lymphotropic virus (HTLV-I and HTLV- 2) and the human immunodeficiency viruses (HIV-1 and HIV-2). In the past, complementing LTCB's pivotal discovery of HTLV-I and -II, we have contributed to the molecular analysis of these genomes. The major findings can be summarized as follows: (1) all adult T-cell leukemia (ATL) cells contain monoclonally integrated HTLV-I; (2) the site of provirus integration is different from patient to patient, suggesting a transacting mechanism for transformation; and (3) presence of a conserved gene, tat, responsible for transcriptional activation. More recently, in collaboration with Warren Leonard (NICHD) and Warner Green's (Duke University) laboratories, we demonstrated that HTLV-I tat turns on expression of IL-2R and IL-2 in T lymphocytes. The target sequences for tat-1 are distinct from those for antigen/mitogen activation. The major efforts of our group at present are directed at studies on the HIVs. The following areas are addressed: (a) analysis of structure and function of the HIV-I genome, with emphasis on the novel accessory genes of this virus; (b) analysis of the env gene, in detail, to define epitopes for neutralization, T4 binding, and viral cytopathic effect (CPE). Of relevance is our group's first demonstration of conserved and non- conserved domains in env; (c) molecular approaches to vaccine development. This work is currently carried out in collaboration with several industrial groups; and (d) comparative analysis of the new virus subgroup, HIV-2, and the related simian virus, STLV-III.
