Role of interferon regulatory factor 7 in T cell responses during acute lymphocytic choriomeningitis virus infection
Department of Medicine, Division of Infectious Diseases and Immunology
Adaptive Immunity; Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Immunity, Innate; Interferon Regulatory Factor-7; Interferon Type I; Lymphocyte Activation; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice; Mice, Inbred C57BL; Mice, Knockout; Signal Transduction; Virus Replication
Type I interferons (IFNs), predominantly IFN-alpha and -beta, play critical roles in both innate and adaptive immune responses against viral infections. Interferon regulatory factor 7 (IRF7), a key innate immune molecule in the type I IFN signaling pathway, is essential for the type I IFN response to many viruses, including lymphocytic choriomeningitis virus (LCMV). Here, we show that although IRF7 knockout (KO) mice failed to control the replication of LCMV in the early stages of infection, they were capable of clearing LCMV infection. Despite the lack of type I IFN production, IRF7 KO mice generated normal CD4(+) T cell responses, and the expansion of naive CD8(+) T cells into primary CD8(+) T cells specific for LCMV GP(33-41) was relatively normal. In contrast, the expansion of the LCMV NP(396)-specific CD8(+) T cells was severely impaired in IRF7 KO mice. We demonstrated that this defective CD8(+) T cell response is due neither to an impaired antigen-presenting system nor to any intrinsic role of IRF7 in CD8(+) T cells. The lack of a type I IFN response in IRF7 KO mice did not affect the formation of memory CD8(+) T cells. Thus, the present study provides new insight into the impact of the innate immune system on viral pathogenesis and demonstrates the critical contribution of innate immunity in controlling virus replication in the early stages of infection, which may shape the quality of CD8(+) T cell responses.
Zhou, Shenghua; Cerny, Anna M.; Fitzgerald, Katherine A.; Kurt-Jones, Evelyn A.; and Finberg, Robert W., "Role of interferon regulatory factor 7 in T cell responses during acute lymphocytic choriomeningitis virus infection" (2012). Infectious Diseases and Immunology Publications and Presentations. 142.