Donati, Matthew Charles; (2002) Analysis of a strain of hepatitis E virus associated with acute liver failure. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Hepatitis E virus (HEV) infection often results in a relatively mild, self-limiting hepatitis, although acute liver failure occurs in some patients, particularly women in the later stages of pregnancy. It is uncertain whether the outcome of infection is predominantly influenced by host or viral factors, or whether an interplay of both is important. At the time of project inception, most HEV sequences in the nucleotide databases were from virus associated with uncomplicated cases of hepatitis E, and many were derived from virus passaged in monkeys. We set out to determine the nucleotide sequence of an HEV strain associated with acute liver failure in a male, using liver tissue as the source of viral RNA. The consensus nucleotide sequence of this HEV strain was determined from standard length amplicon and full length genomic HEV PCR products. Comparison of the consensus sequence with published HEV sequences showed this strain of HEV to conform to the previously described genomic structure. The 5' non-coding region of this strain contained a unique nucleotide change at position 11. There were no obvious features that could account for the increased pathogenicity. The closest matches in the database were with genotype 1 HEV sequences. Expression in-vitro of full length HEV genomes and individual ORF 2 and 3 generated proteins of the size expected from sequence data and published results. Transient expression in COS-7 cells failed to show the presence of HEV specific proteins by western blot or radioimmunoprecipitation or clear evidence of HEV RNA by northern blot. Northern blotting of total liver RNA did not indicate the presence of previously described subgenomic RNAs. The outcome of infection with HEV is likely to be the result of the host immune response rather than altered viral pathogenicity, however further analysis of HEV strains associated with acute liver failure is required.

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