These authors contributed equally to this work.
Lipopolysaccharide-induced innate immune responses in primary hepatocytes downregulates woodchuck hepatitis virus replication via interferon-independent pathways
Article first published online: 2 JUL 2009
© 2009 Blackwell Publishing Ltd
Volume 11, Issue 11, pages 1624–1637, November 2009
How to Cite
Zhang, X., Meng, Z., Qiu, S., Xu, Y., Yang, D., Schlaak, J. F., Roggendorf, M. and Lu, M. (2009), Lipopolysaccharide-induced innate immune responses in primary hepatocytes downregulates woodchuck hepatitis virus replication via interferon-independent pathways. Cellular Microbiology, 11: 1624–1637. doi: 10.1111/j.1462-5822.2009.01353.x
- Issue published online: 8 OCT 2009
- Article first published online: 2 JUL 2009
- Received 18 February, 2009; revised 8 June, 2009; accepted 23 June, 2009.
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.