We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Interferon Regulatory Factor-1 (IRF-1) Shapes Both Innate and CD8<sup>+</sup> T Cell Immune Responses against West Nile Virus Infection.
- Authors
Brien, James D.; Daffis, Stephane; Lazear, Helen M.; Cho, Hyelim; Suthar, Mehul S.; Gale Jr., Michael; Diamond, Michael S.
- Abstract
Interferon regulatory factor (IRF)-1 is an immunomodulatory transcription factor that functions downstream of pathogen recognition receptor signaling and has been implicated as a regulator of type I interferon (IFN)-αβ expression and the immune response to virus infections. However, this role for IRF-1 remains controversial because altered type I IFN responses have not been systemically observed in IRF-1-/- mice. To evaluate the relationship of IRF-1 and immune regulation, we assessed West Nile virus (WNV) infectivity and the host response in IRF-1-/- cells and mice. IRF-1-/- mice were highly vulnerable to WNV infection with enhanced viral replication in peripheral tissues and rapid dissemination into the central nervous system. Ex vivo analysis revealed a cell-type specific antiviral role as IRF-1-/- macrophages supported enhanced WNV replication but infection was unaltered in IRF-1-/- fibroblasts. IRF-1 also had an independent and paradoxical effect on CD8+ T cell expansion. Although markedly fewer CD8+ T cells were observed in nai¨ve animals as described previously, remarkably, IRF-1-/- mice rapidly expanded their pool of WNV-specific cytolytic CD8+ T cells. Adoptive transfer and in vitro proliferation experiments established both cell-intrinsic and cell-extrinsic effects of IRF-1 on the expansion of CD8+ T cells. Thus, IRF-1 restricts WNV infection by modulating the expression of innate antiviral effector molecules while shaping the antigen-specific CD8+ T cell response.
- Publication
PLoS Pathogens, 2011, Vol 7, Issue 9, p1
- ISSN
1553-7366
- Publication type
Academic Journal
- DOI
10.1371/journal.ppat.1002230