| First Author | Maloney NS | Year | 2012 |
| Journal | J Virol | Volume | 86 |
| Issue | 23 | Pages | 12655-64 |
| PubMed ID | 22973039 | Mgi Jnum | J:315821 |
| Mgi Id | MGI:6831338 | Doi | 10.1128/JVI.01564-12 |
| Citation | Maloney NS, et al. (2012) Essential cell-autonomous role for interferon (IFN) regulatory factor 1 in IFN-gamma-mediated inhibition of norovirus replication in macrophages. J Virol 86(23):12655-64 |
| abstractText | Noroviruses (NVs) cause the majority of cases of epidemic nonbacterial gastroenteritis worldwide and contribute to endemic enteric disease. However, the molecular mechanisms responsible for immune control of their replication are not completely understood. Here we report that the transcription factor interferon regulatory factor 1 (IRF-1) is required for control of murine NV (MNV) replication and pathogenesis in vivo. This led us to studies documenting a cell-autonomous role for IRF-1 in gamma interferon (IFN-gamma)-mediated inhibition of MNV replication in primary macrophages. This role of IRF-1 in the inhibition of MNV replication by IFN-gamma is independent of IFN-alphabeta signaling. While the signal transducer and activator of transcription STAT-1 was also required for IFN-gamma-mediated inhibition of MNV replication in vitro, class II transactivator (CIITA), interferon regulatory factor 3 (IRF-3), and interferon regulatory factor 7 (IRF-7) were not required. We therefore hypothesized that there must be a subset of IFN-stimulated genes (ISGs) regulated by IFN-gamma in a manner dependent only on STAT-1 and IRF-1. Analysis of transcriptional profiles of macrophages lacking various transcription factors confirmed this hypothesis. These studies identify a key role for IRF-1 in IFN-gamma-dependent control of norovirus infection in mice and macrophages. |
