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PMID: 20303135 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Lambda and alpha interferons inhibit hepatitis B virus replication through a common molecular mechanism but with different in vivo activities.

Virology ·Vol. 401 ·No. 2 ·2010-06-05 ·Pages 197-206

Pagliaccetti NE, Chu EN, Bolen CR, Kleinstein SH, Robek MD

Abstract

The type III interferons (IFN-lambda1, 2, and 3) induce an antiviral response similar to IFN-alpha/beta, but mediate their activity through a unique receptor. We found that like IFN-alpha/beta, IFN-lambda prevents the assembly of HBV capsids, demonstrating convergence of the two signaling pathways through a single antiviral mechanism. In contrast to IFN-lambda, the structurally related cytokine interleukin (IL)-22 only minimally reduced HBV replication. The transcriptional program activated by IL-22 displayed little similarity to that induced by IFN-lambda, but instead resembled the response elicited by IL-6. We also found that murine IFN-lambda2 had only weak antiviral activity against HBV in the liver of transgenic mice, and that human IFN-lambda2 activity in serum correlated with the sensitivity of the cytokine to proteases. These results demonstrate that the IFN-alpha/beta and IFN-lambda anti-HBV responses operate through a single molecular mechanism, and support the notion that IFN-lambda plays a local, rather than systemic, role in antiviral immunity.

MeSH Terms
Animals Cell Line Cells, Cultured Cytokines/immunology Gene Expression Profiling Hepatitis B virus/immunology,physiology Hepatocytes/virology Humans Interferon-alpha/immunology Interleukins/immunology Mice Mice, Transgenic Oligonucleotide Array Sequence Analysis Virus Replication
Chemicals
Cytokines IFNL2 protein, human Interferon-alpha Interleukins interferon-lambda protein, mouse
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Pagliaccetti Nicole E
Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Chu Esther N
Bolen Christopher R
Kleinstein Steven H
Robek Michael D
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Article Info
Journal
Virology
Abbr.
Virology
ISSN
1096-0341
DOI
10.1016/j.virol.2010.02.022
Published
2010-06-05
Epub
2010-00-29
Pages
197-206
Language
English
Region
United States
NLM ID
0110674
PMCID
PMC2864496
Subset
IM
Grants
NIAID NIH HHS · T32 AI055403 · United States
NIAID NIH HHS · T32 AI007640 · United States
NLM NIH HHS · T15 LM07056 · United States
NCI NIH HHS · R21 CA137067 · United States
NCI NIH HHS · R21 CA137067-01 · United States
External Links
PubMed source DOI: 10.1016/j.virol.2010.02.022 PMC Full Text
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