Sep 14, 2012

Essential cell-autonomous role for interferon (IFN) regulatory factor 1 in IFN-γ-mediated inhibition of norovirus replication in macrophages

Journal of Virology
Nicole S MaloneyHerbert W Virgin

Abstract

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-γ)-mediated inhibition of MNV replication in primary macrophages. This role of IRF-1 in the inhibition of MNV replication by IFN-γ is independent of IFN-αβ signaling. While the signal transducer and activator of transcription STAT-1 was also required for IFN-γ-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-γ 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 iden...Continue Reading

Mentioned in this Paper

Pathogenic Aspects
Microarray Analysis
Pathogenesis
Norovirus (antigen)
Norovirus
Murine
Transcription, Genetic
Virus Replication
Human leukocyte interferon
Interferon Regulatory Factor-7

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