title: Encephalomyocarditis virus 2A protein is required for viral pathogenesis and inhibition of apoptosis.
abstract: The encephalomyocarditis virus (EMCV), a Picornaviridae virus, has a wide host spectrum and can cause various diseases. EMCV virulence factors, however, are as yet ill defined. Here, we demonstrate that the EMCV 2A protein is essential for the pathogenesis of EMCV. Infection of mice with the B279/95 strain of EMCV resulted in acute fatal disease, while the clone C9, derived by serial in vitro passage of the B279/95 strain, was avirulent. C9 harbored a large deletion in the gene encoding the 2A protein. This deletion was incorporated into the cDNA of a pathogenic EMCV1.26 strain. The new virus, EMCV1.26Δ2A, was capable of replicating in vitro, albeit more slowly than EMCV1.26. Only mice inoculated with EMCV1.26 triggered death within a few days. Mice infected with EMCV1.26Δ2A did not exhibit clinical signs, and histopathological analyses showed no damage in the central nervous system, unlike EMCV1.26-infected mice. In vitro, EMCV1.26Δ2A presented a defect in viral particle release correlating with prolonged cell viability. Unlike EMCV1.26, which induced cytopathic cell death, EMCV1.26Δ2A induced apoptosis via caspase 3 activation. This strongly suggests that the 2A protein is required for inhibition of apoptosis during EMCV infection. All together, our data indicate that the EMCV 2A protein is important for the virus in counteracting host defenses, since Δ2A viruses were no longer pathogenic and were unable to inhibit apoptosis in vitro.
authors.affiliation: ANSES, Maisons-Alfort Laboratory for Animal Health, ANSES, INRA, ENVA, UMR 1161 Virology, Maisons-Alfort, France.
authors.forename: M
authors.initials: M
authors.lastname: Carocci
authors.forename: N
authors.initials: N
authors.lastname: Cordonnier
authors.forename: H
authors.initials: H
authors.lastname: Huet
authors.forename: A
authors.initials: A
authors.lastname: Romey
authors.forename: A
authors.initials: A
authors.lastname: Relmy
authors.forename: K
authors.initials: K
authors.lastname: Gorna
authors.forename: S
authors.initials: S
authors.lastname: Blaise-Boisseau
authors.forename: S
authors.initials: S
authors.lastname: Zientara
authors.forename: L Bakkali
authors.initials: LB
authors.lastname: Kassimi
mesh_terms: D000818:Animals; D017209:Apoptosis; D018188:Cardiovirus Infections / Q000473:pathology / Q000821:virology; D002460:Cell Line; D002470:Cell Survival; D002490:Central Nervous System / Q000473:pathology; D006224:Cricetinae; D004195:Disease Models, Animal; D004686:Encephalomyocarditis virus / Q000472:pathogenicity*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D012376:Rodent Diseases / Q000473:pathology / Q000821:virology; D017384:Sequence Deletion; D016019:Survival Analysis; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D057074:Virus Release; D014779:Virus Replication
chemical_list: D050505:Mutant Proteins; D014764:Viral Proteins; D037521:Virulence Factors