Hepatitis E virus (HEV) is a causative agent of acute hepatitis
and jaundice. The number of human infections is approximated
to be over 20 million cases per year. The transmission
is mainly via the fecal-oral route and contaminated water and
food are considered to be a major source of infection. As a
mouse model is not available, a recent development of a cell
culture-adapted HEV strain (47832c) is considered as a very
important tools for molecular analysis of HEV pathogenesis
in cells. Previously, we demonstrated that HEV-encoded methyltransferase
(MeT) encoded by the 47832c strain inhibits
MDA5- and RIG-I-mediated activation of interferon β (IFN-β)
promoter. Here, we report that MeT impairs the phosphorylation
and activation of interferon regulatory factor 3 and the
p65 subunit of NF-κB in a dose-dependent manner. In addition,
the MeT encoded by the 47832c, but not that of HEV
clinical or field isolates (SAR-55, Mex-14, KC-1, and ZJ-1),
displays the inhibitory effect. A deeper understanding of MeTmediated
suppression of IFN-β expression would provide
basis of the cell culture adaptation of HEV.
Citations
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Hepatitis E virus (HEV) is an etiological agent of acute hepatitis
E, a self-limiting disease prevalent in developing countries.
HEV can cause fulminant hepatic failure with high mortality
rates in pregnant women, and genotype 3 is reported to
trigger chronic hepatitis in immunocompromised individuals
worldwide. Screening of plant extracts for compounds with
potential anti-HEV effects led to the identification of a 70%
ethanol extract of Lysimachia mauritiana (LME) that interferes
with replication of the swine HEV genotype 3 replicon.
Furthermore, LME significantly inhibited replication of HEV
genotype 3 and expression of HEV ORF2 in infected cells
without exerting cytotoxic effects. Collectively, our findings
demonstrate the potential utility of LME in the development
of novel antiviral drugs against HEV infection.
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