Peripheral, but not central nervous system, type I interferon expression in mice in response to intranasal vesicular stomatitis virus infection.
Type I interferon (IFN) is critical for resistance of mice to infection with vesicular stomatitis virus (VSV). Wild type (wt) VSV infection did not induce type I IFN production in vitro or in the central nervous system (CNS) of mice; however IFN-beta was detected in lungs, spleen, and serum within 24 h. The M protein mutant VSV, T1026R1 (also referred to as M51R), induced type I IFN production in vitro and in the CNS, with poor expression in spleens. In addition, VSV T1026R1 was not pathogenic to mice after intranasal infection, illustrating the importance of IFN in controlling VSV replication in the CNS. Experiments with chemical sympathectomy, sRAGE, and neutralizing antibody to VSV were performed to investigate the mechanism(s) utilized for induction of peripheral IFN; neither sRAGE infusion nor chemical sympathectomy had an effect on peripheral IFN production. In contrast, administration of neutralizing antibody (Ab) readily blocked the response. Infectious VSV was transiently present in lungs and spleens at 24 h post infection. The results are consistent with VSV traffic from the olfactory neuroepithelium to peripheral lymphoid organs hematogenously or via lymphatic circulation. These results suggest that VSV replicates to high titers in the brains of mice because of the lack of IFN production in the CNS after intranasal VSV infection. In contrast, replication of VSV in peripheral organs is controlled by the production of large amounts of IFN.
Trottier
Mark D
MD
Biology Department, New York University, New York, NY 10003, USA.
Lyles
Douglas S
DS
Reiss
Carol Shoshkes
CS
D000818:Animals; D045744:Cell Line, Tumor; D002490:Central Nervous System / Q000276:immunology; D004195:Disease Models, Animal; D007370:Interferon Type I / Q000235:genetics*; D051379:Mice; D009447:Neuroblastoma; D012333:RNA, Messenger / Q000235:genetics; D054243:Vesicular Stomatitis / Q000276:immunology*
D007370:Interferon Type I; D012333:RNA, Messenger