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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.

Original publication




Journal article


Journal of virology

Publication Date





6221 - 6233


Department of Genetics, University of Edinburgh, Scotland.


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