Arnold, Catherine; (1996) Molecular epidemology of unrelated and related HIV infections. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Sequence data derived from human immunodeficiency virus infection can be used to investigate cases of possible virus transmission between individuals, and to determine phylogenetic relationships of the virus in the general population. The method of recovering the viral genome and the choice of region (gene) for sequencing both influence these analyses. Therefore, multiple single molecules were obtained from infected individuals and both the gp120 and p6/protease sequenced. The set of individuals chosen for sequencing included both related and unrelated HIV-1 infections. The transmission cases investigated were a surgeon and patient, two members of a sex circle, four pairs of heterosexual partners, a mother and child, a needlestick inoculation and an occupational exposure. Analysis of these sequences has allowed establishment of whether apparently epidemiologically connected infections show linkage at the molecular level. These sequences were also used for an assessment of the statistical validity of phylogenetic analyses of using various sub-fragments of gp120, containing differing proportions of conserved and variable regions. These subfragment analyses were compared with complete gp120 and inferences made about the minimum required data set for reliable phylogenies. The data obtained for unrelated infections has been used to investigate the extent of the subtype diversity of HIV-1. It was shown that subtypes A, B, C, D, A/E and G occur in England. These non-B subtypes were obtained from patients in risk groups other than homosexual intercourse. The protein sequences derived from the nucleotide data were used to estimate base substitution rates for gp120. A transition/transversion rate of 1.96 was found for the 51 sequences analysed and the mean synonymous/nonsynonymous ratio for multiple sequences analysed from single individuals was found to be3.86. For comparative purposes, gp120 from chimaeric genomes used to express recombinant proteins were sequenced.

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