title: Alteration of encephalomyocarditis virus pathogenicity due to a mutation at position 100 of VP1.
abstract: Encephalomyocarditis virus (EMCV) infection leads to many diseases including encephalitis, myocarditis and diabetes in its natural host, the mouse. In this study, we generated four cDNA clones with a point mutation at position 100 of VP1. The amino acids isoleucine, alanine, serine and proline were substituted with threonine in the four different clones of EMCV strain BJC3 by site-specific mutagenesis, and viable viruses were rescued. Although all mutants and wild-type viruses display different plaque morphologies, they replicate comparably in BHK-21 cells. The pathogenicity of the mutated viruses was systematically analyzed to investigate the importance of this amino acid in the viral pathogenicity and disease phenotype of EMCV infection in mice. The results showed that the isoleucine- (T1100I) and proline-mutated viruses (T1100P) exhibited a reduced mortality, lower cerebral virus loads and alleviated brain damage while the viruses with serine (T1100S) and alanine (T1100A) substitutions displayed similar properties as the wild-type virus. These findings indicate that the amino acid at position 100 of VP1 is important for EMCV in vivo infection, and its mutation alters the pathogenicity of viral infection in mice.
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhu
authors.forename: XinNa
authors.initials: X
authors.lastname: Ge
authors.forename: XiaoWen
authors.initials: X
authors.lastname: Gong
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: YanHong
authors.initials: Y
authors.lastname: Chen
authors.forename: HanChun
authors.initials: H
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002540:Cerebral Cortex / Q000473:pathology / Q000821:virology; D006224:Cricetinae; D003412:Cricetulus; D004686:Encephalomyocarditis virus / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009205:Myocarditis / Q000401:mortality / Q000473:pathology / Q000821:virology; D017354:Point Mutation; D011897:Random Allocation; D015996:Survival Rate; D019562:Viral Load; D014779:Virus Replication / Q000235:genetics
chemical_list: D036022:Capsid Proteins