Autochthonous hepatitis E in Scotland.

BACKGROUND: Hepatitis E virus is well recognized cause of acute hepatitis. Traditionally hepatitis E virus (HEV) infections were generally associated with travel to Asia and Africa. Autochthonous hepatitis E is recognized as a major cause acute hepatitis in England and Wales. However, autochthonous hepatitis E has never been documented in Scotland. OBJECTIVES: We attempted to determine if autochthonous HEV occurred in Scotland. STUDY DESIGN: Samples from 377 individuals in the South-East of Scotland presenting with acute hepatitis were tested over six years. Acute hepatitis E was confirmed by detecting viraemia or documenting seroconversion and ORF-2 region sequenced. Structured interviews were carried out to identify risk factors for infection. RESULTS: Sixteen individuals (4.2%) had evidence of past HEV infection. Twelve (3.2%) had acute HEV infection, 10 of whom had viraemia (genotype 1=3; genotype 3=7). Of these seven with genotype 3 infection, three had not travelled outside Scotland within the incubation period, while four had travelled to Spain (n=3) or Turkey (n=1). All three individuals with genotype 1 infection had travelled to the Indian subcontinent. CONCLUSIONS: A significant proportion of HEV genotype 3 infections was autochthonous (43%). HEV screening should hence be an integral part of acute hepatitis screening in Scotland, irrespective of the travel history.

Hepatitis E virus mixed infection in immunocompetent patient.

We detected 2 hepatitis E virus (HEV) strains in an acutely infected immunocompetent patient. Two populations of genotype 3 virus were observed in the hypervariable regions and open reading frames 2 and 3, indicating multiple infection with hepatitis E virus. Persons with mixed infections may provide the opportunity for virus recombination.

Evolution of the hepatitis E virus hypervariable region.

The presence of a hypervariable (HVR) region within the genome of hepatitis E virus (HEV) remains unexplained. Previous studies have described the HVR as a proline-rich spacer between flanking functional domains of the ORF1 polyprotein. Others have proposed that the region has no function, that it reflects a hypermutable region of the virus genome, that it is derived from the insertion and evolution of host sequences or that it is subject to positive selection. This study attempts to differentiate between these explanations by documenting the evolutionary processes occurring within the HVR. We have measured the diversity of HVR sequences within acutely infected individuals or amongst sequences derived from epidemiologically linked samples and, surprisingly, find relative homogeneity amongst these datasets. We found no evidence of positive selection for amino acid substitution in the HVR. Through an analysis of published sequences, we conclude that the range of HVR diversity observed within virus genotypes can be explained by the accumulation of substitutions and, to a much lesser extent, through deletions or duplications of this region. All published HVR amino acid sequences display a relative overabundance of proline and serine residues that cannot be explained by a local bias towards cytosine in this part of the genome. Although all published HVRs contain one or more SH3-binding PxxP motifs, this motif does not occur more frequently than would be expected from the proportion of proline residues in these sequences. Taken together, these observations are consistent with the hypothesis that the HVR has a structural role that is dependent upon length and amino acid composition, rather than a specific sequence.