The regulation of human immunodeficiency virus type-1 gene expression

Despite 15 years of intensive research we still do not have an effective treatment for AIDS, the disease caused by human immunodeficiency virus (HIV). Recent research is, however, revealing some of the secrets of the replication cycle of this complex retrovirus, and this may lead to the development of novel antiviral compounds. In particular the virus uses strategies for gene expression that seem to be unique in the eukaryotic world. These involve the use of virally encoded regulatory proteins that mediate their effects through interactions with specific viral target sequences present in the messenger RNA rather than in the proviral DNA. If there are no cellular counterparts of these RNA-dependent gene-regulation pathways then they offer excellent targets for the development of antiviral compounds. The viral promoter is also subject to complex regulation by combinations of cellular factors that may be functional in different cell types and at different cell states. Selective interference of specific cellular factors may also provide a route to inhibiting viral replication without disrupting normal cellular functions. The aim of this review is to discuss the regulation of HIV-1 gene expression and, as far as it is possible, to relate the observations to viral pathogenesis. Some areas of research into the regulation of HIV-1 replication have generated controversy and rather than rehearsing this controversy we have imposed our own bias on the field. To redress the balance and to give a broader view of HIV-1 replication and pathogenesis we refer you to a number of excellent reviews [Cullen, B. R. (1992) Microbiol. Rev. 56, 375-394; Levy, J. A. (1993) Microbiol. Rev. 57, 183-394; Antoni, B. A., Stein, S. & Rabson, A. B. (1994) Adv. Virus Res. 43, 53-145; Rosen, C. A. & Fenyoe, E. M. (1995) AIDS (Phila.) 9, S1-S3].