| First Author | Christensen JE | Year | 2012 |
| Journal | J Virol | Volume | 86 |
| Issue | 13 | Pages | 7384-92 |
| PubMed ID | 22514347 | Mgi Jnum | J:303149 |
| Mgi Id | MGI:6511423 | Doi | 10.1128/JVI.07090-11 |
| Citation | Christensen JE, et al. (2012) Differential impact of interferon regulatory factor 7 in initiation of the type I interferon response in the lymphocytic choriomeningitis virus-infected central nervous system versus the periphery. J Virol 86(13):7384-92 |
| abstractText | Interferon (IFN) regulatory factors (IRFs) are a family of transcription factors involved in regulating type I IFN genes and other genes participating in the early antiviral host response. To better understand the mechanisms involved in virus-induced central nervous system (CNS) inflammation, we studied the influence of IRF1, -3, -7, and -9 on the transcriptional activity of key genes encoding antiviral host factors in the CNS of mice infected with lymphocytic choriomeningitis virus (LCMV). A key finding is that neither IRF3 nor IRF7 is absolutely required for induction of a type I IFN response in the LCMV-infected CNS, whereas concurrent elimination of both factors markedly reduces the virus-induced host response. This is unlike the situation in the periphery, where deficiency of IRF7 almost eliminates the LCMV-induced production of the type I IFNs. This difference is seemingly related to the local environment, as peripheral production of type I IFNs is severely reduced in intracerebrally (i.c.) infected IRF7-deficient mice, which undergo a combined infection of the CNS and peripheral organs, such as spleen and lymph nodes. Interestingly, despite the redundancy of IRF7 in initiating the type I IFN response in the CNS, the response is not abolished in IFN-beta-deficient mice, as might have been expected. Collectively, these data demonstrate that the early type I IFN response to LCMV infection in the CNS is controlled by a concerted action of IRF3 and -7. Consequently this work provides strong evidence for differential regulation of the type I IFN response in the CNS versus the periphery during viral infection. |
