title: Consistent risk group-associated differences in human immunodeficiency virus type 1 vpr, vpu and V3 sequences despite independent evolution.
abstract: Human immunodeficiency virus 1 type vpr, vpu and V3 sequences from 15 homosexual men and 19 intravenous drug users in the Amsterdam Cohort studies were analysed. Previously, we reported that V3 domains of viruses from drug users are distinguishable from those of homosexual men on the basis of two silent mutations. Phylogenetic analysis of vpr, vpu and V3 shows that differences in all three regions correlate with risk group. Two positions in both vpr and vpu were found to differ significantly between the risk groups. The distinguishing positions were confirmed for sequences from 11 Scottish and four German samples. The three regions show relatively independent evolution patterns; they resulted in different phylogenies, the only stable clustering being that based on the risk group distinction. Pairwise differences between sequences of the genes were moderately correlated (around 0.30). Surprisingly, when only silent changes are counted, the correlations dropped almost to zero, indicating that the evolution towards independence was more advanced in the silent than in the non-silent positions. This suggests that selection at the amino acid level is not the primary driving force for the independent evolutionary behaviour of the genes. Recombination, combined with restrictions on certain amino acids because of epistatic interactions between the genes, could be an alternative explanation of this phenomenon.
authors.affiliation: Department of Human Retrovirology, University of Amersterdam, The Netherlands. kuiken@amc.uva.nl
authors.forename: C L
authors.initials: CL
authors.lastname: Kuiken
authors.forename: M T
authors.initials: MT
authors.lastname: Cornelissen
authors.forename: F
authors.initials: F
authors.lastname: Zorgdrager
authors.forename: S
authors.initials: S
authors.lastname: Hartman
authors.forename: A J
authors.initials: AJ
authors.lastname: Gibbs
authors.forename: J
authors.initials: J
authors.lastname: Goudsmit
mesh_terms: D001483:Base Sequence; D015331:Cohort Studies; D004279:DNA, Viral; D005060:Europe / Q000453:epidemiology; D019143:Evolution, Molecular; D016336:Gene Products, vpr / Q000235:genetics*; D005814:Genes, Viral; D014644:Genetic Variation; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006716:Homosexuality; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics*; D010802:Phylogeny; D012307:Risk Factors; D012689:Sequence Homology, Nucleic Acid; D015819:Substance Abuse, Intravenous / Q000150:complications; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics*; D054325:vpr Gene Products, Human Immunodeficiency Virus; D000086082:Viroporin Proteins
chemical_list: D004279:DNA, Viral; D016336:Gene Products, vpr; D015699:HIV Envelope Protein gp120; D054298:Human Immunodeficiency Virus Proteins; D010446:Peptide Fragments; D054334:Viral Regulatory and Accessory Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C059762:HIV envelope protein gp120 (305-321); C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins