| First Author | Thackray LB | Year | 2012 |
| Journal | J Virol | Volume | 86 |
| Issue | 24 | Pages | 13515-23 |
| PubMed ID | 23035219 | Mgi Jnum | J:329771 |
| Mgi Id | MGI:6855135 | Doi | 10.1128/JVI.01824-12 |
| Citation | Thackray LB, et al. (2012) Critical role for interferon regulatory factor 3 (IRF-3) and IRF-7 in type I interferon-mediated control of murine norovirus replication. J Virol 86(24):13515-23 |
| abstractText | Human noroviruses (HuNoV) are the major cause of epidemic, nonbacterial gastroenteritis in the world. The short course of HuNoV-induced symptoms has implicated innate immunity in control of norovirus (NoV) infection. Studies using murine norovirus (MNV) confirm the importance of innate immune responses during NoV infection. Type I alpha and beta interferons (IFN-alpha/beta) limit HuNoV replicon function, restrict MNV replication in cultured cells, and control MNV replication in vivo. Therefore, the cell types and transcription factors involved in antiviral immune responses and IFN-alpha/beta-mediated control of NoV infection are important to define. We used mice with floxed alleles of the IFNAR1 chain of the IFN-alpha/beta receptor to identify cells expressing lysozyme M or CD11c as cells that respond to IFN-alpha/beta to restrict MNV replication in vivo. Furthermore, we show that the transcription factors IRF-3 and IRF-7 work in concert to initiate unique and overlapping antiviral responses to restrict MNV replication in vivo. IRF-3 and IRF-7 restrict MNV replication in both cultured macrophages and dendritic cells, are required for induction of IFN-alpha/beta in macrophages but not dendritic cells, and are dispensable for the antiviral effects of IFN-alpha/beta that block MNV replication. These studies suggest that expression of the IFN-alpha/beta receptor on macrophages/neutrophils and dendritic cells, as well as of IRF-3 and IRF-7, is critical for innate immune responses to NoV infection. |
