Patterns of Mutation Within An Emerging Endemic Lineage of HEV-3a.

The hepatitis E virus can cause chronic infections in immuno-suppressed patients, and cases have been on the rise globally. Viral mutations during such infections are difficult to characterize. We deep sequenced viral populations from 15 immuno-compromised patients with chronic HEV to identify the viral lineage and describe viral mutational hotspots within and across patients. 21 viral RNA samples were collected between 2012-2017 from a single hospital in Singapore. Sequences covering a total of 3894bp of the HEV genome were obtained. Phylogenetic analyses identified all sequences as belonging to the HEV-3a sub-clade and clearly indicate a unique local lineage. Deep sequencing reveals variable viral population complexity during infections. Comparisons of viral samples from the same patients spaced 2-19mths apart revealed rapid nucleotide replacements in the dominant viral sequence in both ribavirin treated and treatment-naive patients. Mutational hotspots were identified within ORF3 and the PCP/HVR domain of ORF1. This article is protected by copyright. All rights reserved.