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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.

Type

Journal article

Journal

J Virol

Publication Date

12/1990

Volume

64

Pages

6221 - 6233

Keywords

Base Sequence, Biological Evolution, Cohort Studies, Factor VIII, Genes, Viral, Genetic Variation, HIV Envelope Protein gp120, HIV Seropositivity, HIV-1, Hemophilia A, Humans, Molecular Sequence Data, Mutation, Oligonucleotide Probes, Phylogeny, Polymerase Chain Reaction, Proviruses, Viral Structural Proteins