title: Cardiovirus leader proteins are functionally interchangeable and have evolved to adapt to virus replication fitness.
abstract: The leader (L) proteins encoded by picornaviruses of the genus Cardiovirus [Theiler's murine encephalomyelitis virus (TMEV) and Encephalomyocarditis virus (EMCV)] are small proteins thought to exert important functions in virus-host interactions. The L protein of persistent TMEV strains was shown to be dispensable for virus replication in vitro, but crucial for long-term persistence of the virus in the central nervous system of the mouse. The phenotype of chimeric viruses generated by exchanging the L-coding regions was analysed and it was shown that the L proteins of neurovirulent and persistent TMEV strains are functionally interchangeable in vitro and in vivo, despite the fact that L is the second most divergent protein encoded by these viruses after the L* protein. The L protein encoded by EMCV and Mengo virus (an EMCV strain) shares about 35 % amino acid identity with that of TMEV. It differs from the latter by lacking a serine/threonine-rich C-terminal domain and by carrying phosphorylated residues not conserved in the TMEV L protein. Our data show that, in spite of these differences, the L protein of Mengo virus shares, with that of TMEV, the ability to inhibit the transcription of type I interferon, cytokine and chemokine genes and to interfere with nucleocytoplasmic trafficking of host-cell proteins. Interestingly, analysis of viral RNA replication of the recombinant viruses raised the hypothesis that L proteins of TMEV and EMCV diverged during evolution to adapt to the different replication fitness of these viruses.
authors.affiliation: Université catholique de Louvain, Christian de Duve Institute of Cellular Pathology, Microbial Pathogenesis Unit, MIPA-VIRO 74-49, 74 avenue Hippocrate, B-1200 Brussels, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Paul
authors.affiliation: Université catholique de Louvain, Christian de Duve Institute of Cellular Pathology, Microbial Pathogenesis Unit, MIPA-VIRO 74-49, 74 avenue Hippocrate, B-1200 Brussels, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Michiels
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D017943:Cardiovirus / Q000737:chemistry / Q000472:pathogenicity / Q000502:physiology*; D018188:Cardiovirus Infections / Q000276:immunology / Q000821:virology*; D002460:Cell Line; D002490:Central Nervous System / Q000821:virology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D051379:Mice; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000096:biosynthesis; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*; D014774:Virulence; D014779:Virus Replication / Q000502:physiology
chemical_list: D016207:Cytokines; D012367:RNA, Viral; D014764:Viral Proteins