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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29AI032415-01A1
Application #
3456062
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1992-07-01
Project End
1997-04-30
Budget Start
1992-07-01
Budget End
1993-04-30
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425