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

Virology. 2010 Jun 5;401(2):197-206. doi: 10.1016/j.virol.2010.02.022. Epub 2010 Mar 29.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Cytokines / immunology*
  • Gene Expression Profiling
  • Hepatitis B virus / immunology*
  • Hepatitis B virus / physiology
  • Hepatocytes / virology
  • Humans
  • Interferon-alpha / immunology*
  • Interleukins / immunology*
  • Mice
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • Virus Replication*

Substances

  • Cytokines
  • interferon-lambda, human
  • Interferon-alpha
  • Interleukins
  • interferon-lambda protein, mouse