title: Does antiretroviral treatment change HIV-1 codon usage patterns in its genes: a preliminary bioinformatics study.
abstract: BACKGROUND
  Codon usage bias has been described for various organisms and is thought to contribute to the regulation of numerous biological processes including viral infections. HIV-1 codon usage has been previously shown to be different from that of other viruses and man. It is evident that the antiretroviral drugs used to restrict HIV-1 replication also select for resistance variants. We wanted to test whether codon frequencies in HIV-1 sequences from treatment-experienced patients differ from those of treatment-naive individuals due to drug pressure affecting codon usage bias.
  
  
  RESULTS
  We developed a JavaScript to determine the codon frequencies of aligned nucleotide sequences. Irrespective of subtypes, using HIV-1 pol sequences from 532 treatment-naive and 52 treatment-experienced individuals, we found that pol sequences from treatment-experienced patients had significantly increased AGA (arginine; p = 0.0002***) and GGU (glycine; p = 0.0001***), and decreased AGG (arginine; p = 0.0001***) codon frequencies. The same pattern was not observed when subtypes B and C sequences were analyzed separately. Additionally, irrespective of subtypes, using HIV-1 gag sequences from 524 treatment-naive and 54 treatment-experienced individuals, gag sequences from treatment-experienced patients had significantly increased CUA (leucine; p < 0.0001***), CAG (glutamine; p = 0.0006***), AUC (isoleucine; p < 0.0001***) and UCU (serine; p = 0.0005***), and decreased AUA (isoleucine; p = 0.0003***) and CAA (glutamine; p = 0.0006***) codon frequencies.
  
  
  CONCLUSIONS
  Using pol and gag genes derived from the same HIV-1 genome, we show that antiretroviral therapy changed certain HIV-1 codon frequencies in a subtype specific way.
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755, Ch. Cote-Ste-Catherine, Montréal, QC, Canada. navastones@gmail.com.|Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montréal, QC, Canada. navastones@gmail.com.|The Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology (HBIGS), University of Heidelberg, Heidelberg, Germany. navastones@gmail.com.|Molecular and Cellular Engineering Group, BioQuant, University of Heidelberg, Heidelberg, Germany. navastones@gmail.com.
authors.forename: Navaneethan
authors.initials: N
authors.lastname: Palanisamy
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755, Ch. Cote-Ste-Catherine, Montréal, QC, Canada.|Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montréal, QC, Canada.
authors.forename: Nathan
authors.initials: N
authors.lastname: Osman
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755, Ch. Cote-Ste-Catherine, Montréal, QC, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ohnona
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755, Ch. Cote-Ste-Catherine, Montréal, QC, Canada.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Xu
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755, Ch. Cote-Ste-Catherine, Montréal, QC, Canada.
authors.forename: Bluma
authors.initials: B
authors.lastname: Brenner
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755, Ch. Cote-Ste-Catherine, Montréal, QC, Canada.
authors.forename: Thibault
authors.initials: T
authors.lastname: Mesplède
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755, Ch. Cote-Ste-Catherine, Montréal, QC, Canada.|Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montréal, QC, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001483:Base Sequence; D003062:Codon; D019295:Computational Biology; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D015751:Genes, pol; D016679:Genome, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics; D016333:HIV Protease / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D010802:Phylogeny; D017421:Sequence Analysis; D014779:Virus Replication / Q000235:genetics; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D003062:Codon; D054301:gag Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus; D019427:HIV Integrase; D016333:HIV Protease
keywords: Antiretroviral therapy; Bioinformatics; Codon usage frequency; HIV-1; Resistance