The IFN regulatory factor 7-dependent type I IFN response is not essential for early resistance against murine cytomegalovirus infection.
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.
Steinberg
Christian
C
II. Medizinische Klinik, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany.
Eisenächer
Katharina
K
Gross
Olaf
O
Reindl
Wolfgang
W
Schmitz
Frank
F
Ruland
Jürgen
J
Krug
Anne
A
D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016898:Interferon-alpha / Q000097:blood; D016899:Interferon-beta / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse; D018664:Interleukin-12; D016899:Interferon-beta; D007371:Interferon-gamma