HIV-1 Modulates the tRNA Pool to Improve Translation Efficiency

  • Anna van Weringh
    Department of Biology, University of Ottawa, Ottawa, Ontario, Canada
  • Manon Ragonnet-Cronin
    Department of Biology, University of Ottawa, Ottawa, Ontario, Canada
  • Erinija Pranckeviciene
    Department of Biology, University of Ottawa, Ottawa, Ontario, Canada
  • Mariana Pavon-Eternod
    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago
  • Lawrence Kleiman
    Lady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada
  • Xuhua Xia
    Department of Biology, University of Ottawa, Ottawa, Ontario, Canada

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<jats:title>Abstract</jats:title><jats:p>Despite its poorly adapted codon usage, HIV-1 replicates and is expressed extremely well in human host cells. HIV-1 has recently been shown to package non-lysyl transfer RNAs (tRNAs) in addition to the tRNALys needed for priming reverse transcription and integration of the HIV-1 genome. By comparing the codon usage of HIV-1 genes with that of its human host, we found that tRNAs decoding codons that are highly used by HIV-1 but avoided by its host are overrepresented in HIV-1 virions. In particular, tRNAs decoding A-ending codons, required for the expression of HIV's A-rich genome, are highly enriched. Because the affinity of Gag-Pol for all tRNAs is nonspecific, HIV packaging is most likely passive and reflects the tRNA pool at the time of viral particle formation. Codon usage of HIV-1 early genes is similar to that of highly expressed host genes, but codon usage of HIV-1 late genes was better adapted to the selectively enriched tRNA pool, suggesting that alterations in the tRNA pool are induced late in viral infection. If HIV-1 genes are adapting to an altered tRNA pool, codon adaptation of HIV-1 may be better than previously thought.</jats:p>

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