Open AccessLipopolysaccharide‐induced innate immune responses in primary hepatocytes downregulates woodchuck hepatitis virus replication via interferon‐independent pathways
Author(s) -
Zhang Xiaoyong,
Meng Zhongji,
Qiu Song,
Xu Yang,
Yang Dongliang,
Schlaak Jörg F.,
Roggendorf Michael,
Lu Mengji
Publication year - 2009
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2009.01353.x
Subject(s) - woodchuck hepatitis virus , biology , interferon , downregulation and upregulation , innate immune system , hepatitis b virus , lipopolysaccharide , mapk/erk pathway , viral replication , virology , immune system , virus , signal transduction , hepadnaviridae , immunology , microbiology and biotechnology , gene , biochemistry
Summary Our previous studies have shown that Toll‐like receptor (TLR) ligands, Poly I:C and lipopolysaccharide (LPS), are able to activate non‐parenchymal liver cells and trigger the production of interferon (IFN) to inhibit hepatitis B virus replication in vivo and in vitro . However, little is known about TLR‐mediated cellular responses in primary hepatocytes. By the model of woodchuck hepatitis virus (WHV) infected primary woodchuck hepatocytes (PWHs), Poly I:C and LPS stimulation resulted in upregulation of cellular antiviral genes and relevant TLRs mRNA expression respectively. LPS stimulation led to a pronounced reduction of WHV replicative intermediates without a significant IFN induction. Poly I:C transfection resulted in the production of IFN and a highly increased expression of antiviral genes in PWHs and slight inhibitory effect on WHV replication. LPS could activate nuclear factor kappa B, MAPK and PI‐3k/Akt pathways in PWHs. Further, inhibitors of MAPK‐ERK and PI‐3k/Akt pathways, but not that of IFN signalling pathway, were able to block the antiviral effect of LPS. These results indicate that IFN‐ independent pathways which activated by LPS are able to downregulate hepadnaviral replication in hepatocytes.