title: Comparison of immune responses to attenuated rabies virus and street virus in mouse brain.
abstract: Rabies is a lethal neurological disease caused by the neurotropic rabies virus (RABV). To investigate the innate immune response in the brain during rabies infection, key gene transcripts indicative of innate immunity in a mouse model system were measured using real-time RT-PCR. Mice were infected via the intracerebral or intramuscular route with either attenuated rabies virus (SRV9) or pathogenic rabies virus (BD06). Infection with SRV9 resulted in the early detection of viral replication and the rapid induction of innate immune response gene expression in the brain. BD06 infection elicited innate immune response gene expression during only the late stage of infection. We measured Na-fluorescein uptake to assess blood-brain barrier (BBB) permeability, which was enhanced during the early stage of SRV9 infection and significantly enhanced during the late stage of BD06 infection. Furthermore, early SRV9 replication increased the maturation and differentiation of dendritic cells (DCs) and B cells in the inguinal lymph nodes and initiated the generation of virus-neutralizing antibodies (VNAs), which cooperate with the innate immune response to eliminate virus from the CNS. However, BD06 infection did not stimulate VNA production; thus, the virus was able to evade the host immune response and cause encephalitis. The rabies virus phosphoprotein has been reported to counteract IFN activation. In an in vitro study of the relationship between IFN antagonism and RABV pathogenicity, we demonstrated that SRV9 more strongly antagonized IFN activity than did BD06. Therefore, there is no positive relationship between the IFN antagonist activity of the virus and its pathogenicity.
authors.affiliation: Laboratory of Epidemiology, Institute of Military Veterinary, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun, 130122, Jilin, China.
authors.forename: Fa-Ming
authors.initials: FM
authors.lastname: Miao
authors.affiliation: Laboratory of Epidemiology, Institute of Military Veterinary, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun, 130122, Jilin, China.
authors.forename: Shou-Feng
authors.initials: SF
authors.lastname: Zhang
authors.affiliation: Laboratory of Epidemiology, Institute of Military Veterinary, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun, 130122, Jilin, China.
authors.forename: Shu-Chao
authors.initials: SC
authors.lastname: Wang
authors.affiliation: Laboratory of Epidemiology, Institute of Military Veterinary, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun, 130122, Jilin, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Epidemiology, Institute of Military Veterinary, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun, 130122, Jilin, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Laboratory of Epidemiology, Institute of Military Veterinary, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun, 130122, Jilin, China. ronglianghu@hotmail.com.
authors.forename: Rong-Liang
authors.initials: RL
authors.lastname: Hu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D057131:Immune Evasion; D007113:Immunity, Innate; D007273:Injections, Intramuscular; D007372:Interferons / Q000037:antagonists & inhibitors; D008198:Lymph Nodes / Q000276:immunology; D008807:Mice, Inbred BALB C; D010539:Permeability; D011818:Rabies / Q000473:pathology*; D011819:Rabies Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D011820:Rabies virus / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D011819:Rabies Vaccines; D007372:Interferons