The IFN regulatory factor 7-dependent type I IFN response is not essential for early resistance against murine cytomegalovirus infection

Eur J Immunol. 2009 Apr;39(4):1007-18. doi: 10.1002/eji.200838814.

Abstract

IFN regulatory factor 7 (IRF7) has been described as the master regulator of type I IFN responses and has been shown to be critical for innate antiviral immunity in vivo. In addition to type I IFN, NK cell responses are involved in the control of viral replication during acute viral infection. To investigate the role of IRF7 in the context of a viral infection that induces a strong NK cell response, the murine cytomegalovirus (MCMV) infection model was used. WT, IRF7-deficient and IRF3/IRF7-double deficient mice were infected with MCMV. The systemic IFN-alpha response to MCMV was entirely dependent on IRF7, but independent of IRF3. However, peak IFN-beta production during MCMV infection was not affected by the lack of IRF7 or both IRF7 and IRF3. Despite the complete lack of IFN-alpha production IRF7- and IRF3/IRF7-deficient mice were surprisingly efficient in controlling MCMV replication and were only modestly more susceptible to MCMV infection than WT mice. NK cell cytotoxicity was unimpaired and NK cell IFN-gamma production was enhanced in IRF7-deficient mice correlating with increased levels of bioactive IL-12. Owing to these compensatory mechanisms IRF7-dependent antiviral immune responses were not essential for resistance against acute MCMV infection in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cytotoxicity, Immunologic / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • Herpesviridae Infections / immunology*
  • Herpesviridae Infections / virology
  • Interferon Regulatory Factor-3 / genetics
  • Interferon Regulatory Factor-3 / immunology
  • Interferon Regulatory Factor-3 / metabolism*
  • Interferon Regulatory Factor-7 / genetics
  • Interferon Regulatory Factor-7 / immunology
  • Interferon Regulatory Factor-7 / metabolism*
  • Interferon-alpha / blood
  • Interferon-beta / blood
  • Interferon-gamma / blood
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / virology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muromegalovirus / immunology*
  • Virus Replication / immunology

Substances

  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • Interferon-alpha
  • Irf3 protein, mouse
  • Irf7 protein, mouse
  • Interleukin-12
  • Interferon-beta
  • Interferon-gamma