Lipopolysaccharide-induced innate immune responses in primary hepatocytes downregulates woodchuck hepatitis virus replication via interferon-independent pathways.
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.
Zhang
Xiaoyong
X
Institute of Virology, Taihe Hospital, Yunyang Medical College, Shiyan, China.
Meng
Zhongji
Z
Qiu
Song
S
Xu
Yang
Y
Yang
Dongliang
D
Schlaak
Jörg F
JF
Roggendorf
Michael
M
Lu
Mengji
M
D000818:Animals; D002478:Cells, Cultured; D017919:Hepatitis B Virus, Woodchuck / Q000276:immunology* / Q000502:physiology*; D022781:Hepatocytes / Q000276:immunology*; D007372:Interferons / Q000096:biosynthesis / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008392:Marmota; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology; D015398:Signal Transduction; D014779:Virus Replication
D008070:Lipopolysaccharides; D016328:NF-kappa B; D007372:Interferons; D019869:Phosphatidylinositol 3-Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D011070:Poly I-C