Retroviruses have been linked to two diseases in man, leukemia and AIDS. Human immunodeficiency virus type 1 (HIV-1) has been identified as etiologic agent of AIDS. This virus contains several regulatory genes whose functions are crucial for viral replication. The ultimate function of one of these proteins, Rev, is to increase the levels of protein expressed from those MRNAS that contain a cis-acting Rev-responsive element (RRE).
The Specific Aims of this proposal address the genetic and biochemical basis of rev gene function in regards to the translation of RRE-containing RNAs. element which play We will use mutagenesis studies to dissect the genetic to a role in the translation of cytoplasmic Rev-dependent MRNAS (Aim 1). These mutants will be assayed for effects on cellular, RNA distribution and protein expression. To determine whether the translational effect of Rev exhibits any cell - or construct-specific effect, subgenomic and genomic constructs will be compared in various lymphoid and non-lymphoid cell- types (Aim 2). Biochemical studies will be performed to attempt to further characterize the complex formed with non-translated HIV-1 RNAs in the absence of Rev (Aim 3). It is expected that by further understanding the regulation of gene expression of HIV-1, insight into how to exert control over the growth of human retroviruses my be gained. If one is able to interfere with the growth of these retroviruses, the severity of disease associated with retroviral infection may be ameliorated.
| Campbell, L H; Borg, K T; Haines, J K et al. (1994) Human immunodeficiency virus type 1 Rev is required in vivo for binding of poly(A)-binding protein to Rev-dependent RNAs. J Virol 68:5433-8 |
