Control of herpes simplex virus replication is mediated through an interferon regulatory factor 3-dependent pathway.
The type I interferon (IFN) cascade is critical in controlling viral replication and pathogenesis. Recognition pathways triggered by viral infection rapidly induce the type I IFN cascade, often in an IFN regulatory factor 3 (IRF-3)-dependent fashion. This dependence predicts that loss of IRF-3 would render early recognition pathways inoperative and thereby impact virus replication, but this has not been observed previously with herpes simplex virus type 1 (HSV-1) in vitro. In this study, HSV-1-infected IRF-3(-/-) bone marrow-derived dendritic cells (BMDCs) and macrophages supported increased HSV replication compared to control cells. In addition, IRF-3-deficient BMDCs exhibited delayed type I IFN synthesis compared to control cells. However, while IFN pretreatment of IRF-3(-/-) BMDCs resulted in reduced virus titers, a far greater reduction was seen after IFN treatment of wild-type cells. This suggests that even in the presence of exogenously supplied IFN, IRF-3(-/-) BMDCs are inherently defective in the control of HSV-1 replication. Together, these results demonstrate a critical role for IRF-3-mediated pathways in controlling HSV-1 replication in cells of the murine immune system.
Menachery
Vineet D
VD
Departments of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Missouri, 63110, USA.
Leib
David A
DA
D000818:Animals; D003713:Dendritic Cells / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000502:physiology*; D050838:Interferon Regulatory Factor-3 / Q000172:deficiency / Q000276:immunology*; D008264:Macrophages / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014779:Virus Replication
D050838:Interferon Regulatory Factor-3