Abstract
Discovery of the link between human T-cell leukemia virus type I (HTLV-I) and adult T-cell leukemia, and the emergence of the acquired immunodeficiency syndrome, in association with human immunodeficiency virus type 1 (HIV-1) has led to intense investigation of underlying mechanisms of pathogenesis and retroviral gene regulation. In contrast to avian and murine RNA viruses previously studied, the human oncogenic retroviruses HTLV-I/II, as well as the Lentivirus family, represented by HIV-1, HIV-2, and SIV, demonstrated genomes of increased complexity, encoding multiple mRNA species in contrast to the simpler avian/murine species. “Simple” retroviruses generally encode two mRNA species, unspliced gag/pol, and singly spliced env mRNA, while additional splicing events result in as many as eight identifiable mRNA species for HTLV-1, encoding at least two, and potentially up to five, additional proteins (Myers and Pavlakis 1991). For HIV-1, an exceptionally complex pattern of transcripts is observed, resulting in up to 20 different mRNAs and ten or more different proteins (Myers and Pavlakis 1991; Schwartz et al. 1990). Several of the proteins encoded by the novel spliced mRNAs in HTLV-I/II and HIV-1/HIV-2 act as regulators, both transcriptional and posttranscriptional, of viral gene expression. By definition, these trans-acting regulatory proteins interact with both cis-acting viral sequences, as well as with cellular regulatory machinery to alter viral gene expression. Researchers have therefore focused attention on possible cellular regulatory consequences of retro-viral gene expression.