title: On the primer binding site mutation that appears and disappears during HIV and SIV replication.
abstract: A recent study by Fennessey et al. (Retrovirology 12:49, 2015) described the optimization of a popular SIV clone by removal of four suboptimal point mutations. One of these mutations is present in a non-coding part of the viral genome and is probed in that study in more detail because of some fascinating properties. This primer binding site (PBS) mutation reverts rapidly to the wild-type sequence, which the authors interpret as indicating that this mutation exerts a profound fitness impact. The authors proposed the involvement of a cellular DNA repair mechanism in the reversion. Furthermore, it was suggested that premature termination of reverse transcription can explain why some of the viral progeny still contained the mutant sequence. However, we argue that all these special properties are a direct consequence of the unique nature of the viral PBS motif. The PBS binds the tRNA primer for reverse transcription and the viral progeny inherits either the sequence of the cellular tRNA or the PBS sequence of the viral RNA genome. The presence of a variant tRNA species explains the rapid appearance and disappearance of a variant PBS sequence.
authors: Department of Medical Microbiology, Laboratory of Experimental Virology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands. b.berkhout@amc.uva.nl.
authors: Ben
authors: B
authors: Berkhout
authors: Department of Medical Microbiology, Laboratory of Experimental Virology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands. a.t.das@amc.uva.nl.
authors: Atze T
authors: AT
authors: Das
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D056084:Genetic Fitness; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D017354:Point Mutation; D012357:RNA, Transfer, Lys / Q000235:genetics; D038621:Regulatory Sequences, Ribonucleic Acid; D048348:Reverse Transcription; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000502:physiology; D014779:Virus Replication / Q000235:genetics
chemical_list: D012357:RNA, Transfer, Lys; D038621:Regulatory Sequences, Ribonucleic Acid