A CRITICAL ROLE FOR THE TAR ELEMENT IN PROMOTING EFFICIENT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE TRANSCRIPTION

The regulation of human immunodeficiency virus type 1 (HIV-I) gene exp ression is dependent on the transactivator protein Tat and an RNA elem ent extending from the transcription initiation site to +57 known as T AR. TAR forms a stable RNA secondary structure which is critical for h igh levels of HIV-1 gene expression and efficient viral replication. U sing a genetic approach, we isolated HIV-1 mutants in TAR that were co mpetent for high levels of gene expression but yet were markedly defec tive for viral replication, Single-cycle infections with these viruses demonstrated that they were defective in the initiation of reverse tr anscription. Additional mutational analysis revealed a variety of othe r HIV-1 TAR mutants with the same defective phenotype. Thus, in additi on to the well-characterized role of the primer binding site, other RN A elements within the HIV-1 genome are also critical in the regulation of reverse transcription. These studies demonstrate that HIV-1 TAR RN A is a key regulator of the reverse transcription and illustrate how a unique RNA structure can modulate diverse regulatory processes in the HIV-I life cycle crucial for efficient viral replication.