Hepatitis E virus (HEV) is one of the causative agents for
liver inflammation worldwide. The open reading frame 4 (ORF4) has been
demonstrated to enhance the replication in HEV Genotype 1 (G1) isolates through
regulation of an internal ribosome entry site (IRES)-like RNA element. HEV
accounts for up to 30% mortality rate in pregnant women with the highest
incidences reported for HEV G1. The HEV physiopathogenesis and adaptation to
new hosts are attributed to its large genomic variability and constant evolution.
Although previous investigations have reported extensive genetic diversity in
HEV strains, data on the prevalence of genomic variability in ORF4 protein
remains unexplored. The present study attempted a detailed characterization of
the factors contributing to genetic variability in HEV ORF4 which included
mutational, entropy and selection pressure analyses. The sequences of ORF4
genomes were retrieved and a total of three different datasets were built,
representative of each host Human, Rat and Ferret, and comparative analyses
were performed. Resulting alignments of ORF4 protein genes inspected for
different datasets revealed the prevalence of both synonymous and
non-synonymous mutations. Datasets I, II and III were observed with 1, 63 and
23 entropy sites, respectively, with Dataset I possessing the least variation
and Dataset II with the largest variation. Several non-synonymous mutations in
conjunction with higher entropy values were observed in the II (Rat) and III
(Ferret) datasets, however, limited variation was observed in the I dataset
(Human). Selection pressure analysis revealed ORF4 protein genes under both
purifying (I) and positive (II and III) selection. A higher transition to
transversion ratio was observed signifying bias towards transition in ORF4
genomes. This chapter aims to collect information and discuss new advances in
the role of ORF4 heterogeneity in HEV variability. These findings are likely to
augment information about the molecular evolution, adaptation and biology of
this emerging viral protein.
Author(s) Details
Zoya Shafat
Centre for Interdisciplinary Research in Basic Sciences,
Jamia Millia Islamia, New Delhi 110025, India.
Please see the link:- https://doi.org/10.9734/bpi/mono/978-81-976932-1-2/CH4
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