title: Concurrent evolution of human immunodeficiency virus type 1 in patients infected from the same source: rate of sequence change and low frequency of inactivating mutations.
abstract: Direct sequencing of segments of the envelope gene of human immunodeficiency virus type 1 proviruses in peripheral blood mononuclear cells has revealed that a cohort of hemophiliacs who were infected after exposure to a single common batch of factor VIII share closely related virus strains. Seventy-four sequences extending from hypervariable regions V4 through V5 from nine patients yielded a mean intrapatient nucleotide distance of 5.5%, while a mean of 4.2% was observed in 39 sequences of the V3 loop (six patients). Phylogenetic analysis revealed that sequences of six Edinburgh patients were particularly closely related and those from a patient infected in the United States were very distinct. The mean nucleotide distance among these six was 8.3%, while the mean distance from the U.S.-derived sequences was 25.5% in the V4-V5 region. The rate of sequence change across this patient group has been estimated to be 0.4% per year in the V4-V5 region and 0.5% per year in the V3 region, with at least a twofold range across patients. Only two inactivating nucleotide substitutions have been observed in a total of 42 kb of sequence obtained from the env and gag genes during this study.
authors.affiliation: Department of Genetics, University of Edinburgh, Scotland.
authors.forename: P
authors.initials: P
authors.lastname: Balfe
authors.forename: P
authors.initials: P
authors.lastname: Simmonds
authors.forename: C A
authors.initials: CA
authors.lastname: Ludlam
authors.forename: J O
authors.initials: JO
authors.lastname: Bishop
authors.forename: A J
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D001483:Base Sequence; D005075:Biological Evolution; D015331:Cohort Studies; D005169:Factor VIII / Q000627:therapeutic use; D005814:Genes, Viral; D014644:Genetic Variation; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D006679:HIV Seropositivity; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006467:Hemophilia A / Q000150:complications / Q000382:microbiology / Q000628:therapy; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification; D015678:Viral Structural Proteins / Q000235:genetics*
chemical_list: D015699:HIV Envelope Protein gp120; D015345:Oligonucleotide Probes; D015678:Viral Structural Proteins; D005169:Factor VIII