Genetic diversity and evolution of hepatitis C virus

Harris, Kathryn Ann (2000). Genetic diversity and evolution of hepatitis C virus. PhD thesis The Open University.



Inter- and intra-host Hey variation was investigated. First. a polymerase chain reactionrestriction fragment length polymorphism procedure was used to assign genotypes and subtypes to Hey infecting 567 individuals (comprising haemophilia patients, blood donors, intravenous drug users, attenders of antenatal and genito-urinary medicine clinics and chronic liver disease patients) from England and Wales. The majority of infections were associated with types 3a, 1 a and 1 b, and genotype distributions were generally similar in different sub-populations. Only 1 % of individuals were identified as being infected with more than one subtype. The intra-host variability of Hey in a selection of haemophilia patients, blood donors and intravenous drug users was then studied. For each individual, peR clones derived from the NS5b and 5' non-coding regions of the Hey genome were screened for sequence differences by denaturing gradient gel electrophoresis (DGGE) and nucleotide sequencing. The complexity and diversity of Hey quasi species, though differing between individuals, could not be correlated with the risk group to which the study patients belonged. Furthermore, no mixed genotype or subtype infections were identified. Thus the hypothesis that multiply exposed individuals are infected with a greater variety of HCY variants could not be substantiated. The DGGE procedure was further used to investigate the hypothesis that HCY genetic evolution occurs uniformly in patients during the acute phase of infection. Changes in diversity in the HCY hypervariable region 1 in individuals undergoing seroconversion were observed to differ between patients, thereby negating that hypothesis. Moreover, in a given individual, Hey could be subjected to either positive or negative selective pressure. Thus, factors other than the acute-phase host response determine the course of Hey genetic evolution.

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