Structural and functional evidence that initiation and elongation of HIV-1 reverse transcription are distinct processes

• Published in: Biochimie Vol. 78; no. 11; pp. 1087 - 1096
• Main Authors: Lanchy, J.M., Isel, C., Ehresmann, C., Marquet, R., Ehresmann, B.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 1996; Elsevier
• Subjects: AIDS/HIV; Base Sequence; Biochemistry, Molecular Biology; HIV; HIV Reverse Transcriptase - metabolism; HIV-1 - genetics; HIV-1 - metabolism; Human immunodeficiency virus 1; Humans; Life Sciences; Molecular Sequence Data; Nucleic Acid Conformation; polymerase; Retroviridae - metabolism; retrovirus; reverse transcriptase; RNA, Transfer, Amino Acyl - biosynthesis; RNA, Transfer, Amino Acyl - chemistry; RNA, Viral - biosynthesis; RNA, Viral - chemistry; Transcription, Genetic; tRNA 3Lys; HIV-1; PBS; SIV; retrovirus; RT; HIV-2; reverse transcriptase; polymerase; AMV; LTR; FIV; HIV; RSV; MLV; tRNA 3 Lys; ODN; EIAV; NCp; RNase H; utRNA 3 Lys; tRNA
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/S0300-9084(97)86734-X

Retroviral reverse transcription starts with the extension of a cellular tRNA primer bound near the 5′ end of the viral genomic RNA at a site called the primer binding site (PBS). Formation of the HIV-1 initiation complex between tRNA 3 Lys, viral RNA and reverse transcriptase probably occurs during encapsidation of these components. tRNA 3 Lys is thought to be selectively packaged by interaction with the reverse transcriptase domain of the Pr160 Gag-Pol precursor protein, then annealed to the PBS of viral RNA with the help of the nucleocapsid protein. tRNA 3 Lys and HIV-1 viral RNA form a highly-structured complex, with extended interactions between the two molecules. Two different modes of reverse transcription have been distinguished: initiation, a tRNA 3 Lys-specific and distributive mode of polymerization corresponding to the addition of the first five nucleotides, followed by elongation, a non-specific and processive mode of DNA synthesis. These two modes are reminiscent of the initiation and elongation processes previously observed with DNA-dependent RNA polymerases.