Alternative tRNA priming of human immunodeficiency virus type 1 reverse transcription explains sequence variation in the primer-binding site that has been attributed to APOBEC3G activity.
It is generally assumed that human immunodeficiency virus type 1 (HIV-1) uses exclusively the cellular tRNA(3)(Lys) molecule as a primer for reverse transcription. We demonstrate that HIV-1 uses not only tRNA(3)(Lys) but also an alternative tRNA primer. This tRNA was termed tRNA(5)(Lys), and the near completion of the human genome project has allowed the identification of four tRNA(5)(Lys)encoding genes. Priming with tRNA(5)(Lys) results in a single nucleotide polymorphism in the viral primer-binding site that is present in multiple natural and laboratory HIV isolates. This sequence variation was recently attributed to APOBEC3G activity. However, our results show that alternative tRNA priming can cause this mutation in the absence of APOBEC3G.
Das
Atze T
AT
Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Vink
Monique
M
Berkhout
Ben
B
D000071480:APOBEC-3G Deaminase; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D003564:Cytidine Deaminase; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009700:Nucleoside Deaminases; D011506:Proteins / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012357:RNA, Transfer, Lys / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins; D048348:Reverse Transcription; D012689:Sequence Homology, Nucleic Acid; D014779:Virus Replication
D011506:Proteins; C034477:RNA primers; D012357:RNA, Transfer, Lys; D012097:Repressor Proteins; D012313:RNA; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase