title: Rabies virus glycoprotein is an important determinant for the induction of innate immune responses and the pathogenic mechanisms.
abstract: Our previous studies have suggested that street and fixed rabies viruses (RABVs) induce diseases in the mouse model via different mechanisms. In the present study, attempts were made to determine if it is the glycoprotein (G) that is responsible for the observed differences in the pathogenic mechanisms. To this end, an infectious clone from fixed virus B2c was established and used as a backbone for exchange of the G from street viruses. The rate of viral replication, expression of viral proteins, and the induction of innate immune responses were compared in cells or in mice infected with each of the viruses. Furthermore, the infiltration of inflammatory cells into the CNS and the enhancement of blood-brain barrier (BBB) permeability were also compared. It was found that fixed viruses induced stronger innate immune responses (expression of chemokines, infiltration of inflammatory cells, and enhancement of BBB permeability) than street RABV or recombinant viruses expressing the G from street RABVs. Fixed viruses induce disease via an immune-mediated pathogenic mechanism while street viruses or recombinant viruses expressing the G from street RABVs induce diseases via a mechanism other than immune-mediated pathogenesis. Therefore, RABV G is an important determinant for the induction of innate immune responses and consequently the pathogenic mechanisms.
authors.affiliation: Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: Hualei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: Fazal
authors.initials: F
authors.lastname: Mahmood
authors.affiliation: Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA; State-Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: zhenfu@uga.edu.
authors.forename: Zhen F
authors.initials: ZF
authors.lastname: Fu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000956:Antigens, Viral / Q000276:immunology*; D001812:Blood-Brain Barrier / Q000276:immunology / Q000473:pathology / Q000821:virology; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000821:virology; D018925:Chemokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D011818:Rabies / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D011820:Rabies virus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D018925:Chemokines; D006023:Glycoproteins; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus