@article{mbs:/content/journal/jgv/10.1099/vir.0.81642-0, author = "Paul, Sophie and Michiels, Thomas", title = "Cardiovirus leader proteins are functionally interchangeable and have evolved to adapt to virus replication fitness", journal= "Journal of General Virology", year = "2006", volume = "87", number = "5", pages = "1237-1246", doi = "https://doi.org/10.1099/vir.0.81642-0", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.81642-0", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", 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.", }