HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fernández, M. Articles by Carreño, V. Search for Related Content PubMed PubMed Citation Articles by Fernández, M. Articles by Carreño, V. Agricola Articles by Fernández, M. Articles by Carreño, V.

Hepatitis B virus downregulates the human interferon-inducible MxA promoter through direct interaction of precore/core proteins

Mario Fernández

Fundación para el Estudio de las Hepatitis Virales, C/Guzmán el Bueno 72, 28015 Madrid, Spain

Correspondence
Vicente Carreño
fehvhpa{at}fehv.org

The human MxA protein is an interferon (IFN)-inducible GTPase with proven antiviral activity against diverse viruses. IFN responsiveness is impaired in chronic hepatitis B virus (HBV) infection. Accordingly, initial experiments showed that, in contrast to parental HepG2 cells, when HepG2-derived 2.2.15 liver cells carrying the HBV genome were treated with IFN, they could not synthesize the MxA protein. Furthermore, MxA expression was reduced in HepG2 cells transiently transfected with the HBV genome. To assess whether HBV-encoded precore/core (preC/C) proteins interact with the IFN-signalling pathway, HepG2, Chang and HeLa cells were transfected with preC/C expression plasmids; the levels of signal transducers remained unaffected. Next, full-length and deletion mutants fused to the CAT reporter gene were tested to investigate whether MxA inhibition occurs at the promoter level. In co-transfection experiments, IFN-induced CAT activity was inhibited by preC/C expression in a dose-dependent manner. Analysis of deletion mutants showed that the region affected by the preC/C proteins comprises IFN-stimulated response elements 2 and 3, upstream of the putative start codon of the MxA promoter. In addition, HBV preC/C proteins interacted directly with the MxA promoter, as shown by electrophoretic mobility shift assays. These results demonstrate a mechanism that HBV probably uses to downregulate an element of the IFN-induced host antiviral responses, which accounts for the impairment observed in HBV-infected patients.

Present address: Cancer Research UK Molecular Oncology Unit, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK.

This article has been cited by other articles:

				T. D. Carroll, S. R. Matzinger, M. Genesca, L. Fritts, R. Colon, M. B. McChesney, and C. J. Miller Interferon-Induced Expression of MxA in the Respiratory Tract of Rhesus Macaques Is Suppressed by Influenza Virus Replication J. Immunol., February 15, 2008; 180(4): 2385 - 2395. [Abstract] [Full Text] [PDF]

				R. E. Randall and S. Goodbourn Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures J. Gen. Virol., January 1, 2008; 89(1): 1 - 47. [Abstract] [Full Text] [PDF]

				M. Wu, Y. Xu, S. Lin, X. Zhang, L. Xiang, and Z. Yuan Hepatitis B virus polymerase inhibits the interferon-inducible MyD88 promoter by blocking nuclear translocation of Stat1 J. Gen. Virol., December 1, 2007; 88(12): 3260 - 3269. [Abstract] [Full Text] [PDF]