Hayman, Anna; (2002) The biodiversity of human immunodeficiency virus type 1: Evolution during primary infection and transmission. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

One of the most notable features of the human immunodeficiency virus (HIV) is the high level of variability, both between patients and within infected individuals. This diversity enables the virus to evolve rapidly, altering both its pathogenicity and tissue tropism. Furthermore, the virus can evade neutralisation both by the host immune system and by anti-retroviral drugs, presenting a huge challenge for patient therapy and vaccine design. This thesis is a detailed investigation into the variation and evolution of env gp120, the most variable region of the viral genome. Two different aspects are discussed. Firstly, a heterosexual transmission cluster in a town in the north of England is described, including 15 patients. The molecular epidemiology illustrates that HIV-1 subtype B is well established in this community and that this subtype is perfectly capable of establishing a heterosexual epidemic. Two distinct related clusters were identified, further studies indicated the presence of R5 and R5X4 strains in each group respectively. Interestingly, the patients were also divided into the same two groups on the basis of clinical and epidemiological information. Secondly, events taking place during early infection were studied. Two time points from eight seroconvertors were investigated, the first available sample after diagnosis and a time point 2-3 weeks later. Complete env gp120s from DNA and RNA populations were sequenced. Genetic diversity varied between the patients, the majority harbouring homogenous populations, although 2/8 were heterogenous. Length changes in the V1-V2 region were a common feature, possibly as a consequence of viral escape from immune selection. Together these studies give more insight into the biological consequences of the genetic diversity of HIV-1, with respect to transmission and primary infection.

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