title: Genome-Wide Transcriptional Profiling Reveals Two Distinct Outcomes in Central Nervous System Infections of Rabies Virus.
abstract: Rabies remains a major public health concern in many developing countries. The precise neuropathogenesis of rabies is unknown, though it is hypothesized to be due to neuronal death or dysfunction. Mice that received intranasal inoculation of an attenuated rabies virus (RABV) strain HEP-Flury exhibited subtle clinical signs, and eventually recovered, which is different from the fatal encephalitis caused by the virulent RABV strain CVS-11. To understand the neuropathogenesis of rabies and the mechanisms of viral clearance, we applied RNA sequencing (RNA-Seq) to compare the brain transcriptomes of normal mice vs. HEP-Flury or CVS-11 intranasally inoculated mice. Our results revealed that both RABV strains altered positively and negatively the expression levels of many host genes, including genes associated with innate and adaptive immunity, inflammation and cell death. It is found that HEP-Flury infection can activate the innate immunity earlier through the RIG-I/MDA-5 signaling, and the innate immunity pre-activated by HEP-Flury or Newcastle disease virus (NDV) infection can effectively prevent the CVS-11 to invade central nervous system (CNS), but fails to clear the CVS-11 after its entry into the CNS. In addition, following CVS-11 infection, genes implicated in cell adhesion, blood vessel morphogenesis and coagulation were mainly up-regulated, while the genes involved in synaptic transmission and ion transport were significantly down-regulated. On the other hand, several genes involved in the MHC class II-mediated antigen presentation pathway were activated to a greater extent after the HEP-Flury infection as compared with the CVS-11 infection suggesting that the collaboration of CD4(+) T cells and MHC class II-mediated antigen presentation is critical for the clearance of attenuated RABV from the CNS. The differentially regulated genes reported here are likely to include potential therapeutic targets for expanding the post-exposure treatment window for RABV infection.
authors.affiliation: College of Veterinary Medicine, South China Agricultural UniversityGuangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South China Agricultural UniversityGuangzhou, China.
authors.forename: Daiting
authors.initials: D
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.
authors.forename: Feilong
authors.initials: F
authors.lastname: He
authors.affiliation: School of Food Science, Guangdong Pharmaceutical University Zhongshan, China.
authors.forename: Shuilian
authors.initials: S
authors.lastname: Bi
authors.affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.
authors.forename: Huixia
authors.initials: H
authors.lastname: Guo
authors.affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.
authors.forename: Baoshi
authors.initials: B
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, South China Agricultural UniversityGuangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South China Agricultural UniversityGuangzhou, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: College of Veterinary Medicine, South China Agricultural UniversityGuangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South China Agricultural UniversityGuangzhou, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Liang
authors.affiliation: College of Veterinary Medicine, South China Agricultural UniversityGuangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South China Agricultural UniversityGuangzhou, China.
authors.forename: Youtian
authors.initials: Y
authors.lastname: Yang
authors.affiliation: College of Veterinary Medicine, South China Agricultural UniversityGuangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South China Agricultural UniversityGuangzhou, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Tian
authors.affiliation: College of Veterinary Medicine, South China Agricultural UniversityGuangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South China Agricultural UniversityGuangzhou, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Ju
authors.affiliation: College of Veterinary Medicine, South China Agricultural UniversityGuangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South China Agricultural UniversityGuangzhou, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Fan
authors.affiliation: College of Veterinary Medicine, South China Agricultural UniversityGuangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South China Agricultural UniversityGuangzhou, China.
authors.forename: Jinding
authors.initials: J
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, South China Agricultural UniversityGuangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South China Agricultural UniversityGuangzhou, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Guo
authors.affiliation: College of Veterinary Medicine, South China Agricultural UniversityGuangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South China Agricultural UniversityGuangzhou, China.
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Luo
keywords: MHC class II; innate immunity; pathogenesis; pathogenic and attenuated strains; rabies virus; transcriptome