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-1) gene expression is dependent on the transactivator protein Tat and an RNA element extending from the transcription initiation site to +57 known as TAR. TAR forms a stable RNA secondary structure which is critical for high levels of HIV-1 gene expression and efficient viral replication. Using a genetic approach, we isolated HIV-1 mutants in TAR that were competent for high levels of gene expression but yet were markedly defective for viral replication. Single-cycle infections with these viruses demonstrated that they were defective in the initiation of reverse transcription. Additional mutational analysis revealed a variety of other HIV-1 TAR mutants with the same defective phenotype. Thus, in addition to the well-characterized role of the primer binding site, other RNA elements within the HIV-1 genome are also critical in the regulation of reverse transcription. These studies demonstrate that HIV-1 TAR RNA is a key regulator of the reverse transcription and illustrate how a unique RNA structure can modulate diverse regulatory processes in the HIV-1 life cycle crucial for efficient viral replication.
Harrich
D
D
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8594, USA.
Ulich
C
C
Gaynor
R B
RB
D001483:Base Sequence; D002460:Cell Line; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000032:analysis; D014779:Virus Replication
D012367:RNA, Viral; D014764:Viral Proteins