Forced selection of a human immunodeficiency virus type 1 variant that uses a non-self tRNA primer for reverse transcription: involvement of viral RNA sequences and the reverse transcriptase enzyme

Journal of Virology
Truus E M AbbinkB Berkhout

Abstract

Human immunodeficiency virus type 1 uses the tRNA(3)(Lys) molecule as a selective primer for reverse transcription. This primer specificity is imposed by sequence complementarity between the tRNA primer and two motifs in the viral RNA genome: the primer-binding site (PBS) and the primer activation signal (PAS). In addition, there may be specific interactions between the tRNA primer and viral proteins, such as the reverse transcriptase (RT) enzyme. We constructed viruses with mutations in the PAS and PBS that were designed to employ the nonself primer tRNA(Pro) or tRNA(1,2)(Lys). These mutants exhibited a severe replication defect, indicating that additional adaptation of the mutant virus is required to accommodate the new tRNA primer. Multiple independent virus evolution experiments were performed to select for fast-replicating variants. Reversion to the wild-type PBS-lys3 sequence was the most frequent escape route. However, we identified one culture in which the virus gained replication capacity without reversion of the PBS. This revertant virus eventually optimized the PAS motif for interaction with the nonself primer. Interestingly, earlier evolution samples revealed a single amino acid change of an otherwise well-conserved...Continue Reading

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Citations

May 4, 2006·Nucleic Acids Research·Pavlina KonstantinovaBen Berkhout
Jan 18, 2012·Retrovirology·Antoinette C van der Kuyl
Mar 28, 2006·FEBS Letters·Ben Berkhout, Joost Haasnoot
Feb 8, 2008·Virus Research·Truus E M Abbink, Ben Berkhout
Feb 25, 2014·Journal of Biomolecular Structure & Dynamics·Irina N KolomietsDmytro M Hovorun
Nov 22, 2008·Journal of Molecular Biology·Stefan G SarafianosEddy Arnold
Jan 1, 2010·Viruses·Catherine IselRoland Marquet
Nov 11, 2017·Nucleic Acids Research·Lukasz J KielpinskiJeppe Vinther
Apr 6, 2019·Retrovirology·Christine M FennesseyBrandon F Keele

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