Cardiovirus Leader Proteins Are Functionally Interchangeable and Have Evolved to Adapt to Virus Replication Fitness

J Gen Virol. 2006 May;87(Pt 5):1237-46. doi: 10.1099/vir.0.81642-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Amino Acid Sequence
  • Animals
  • Cardiovirus / chemistry
  • Cardiovirus / pathogenicity
  • Cardiovirus / physiology*
  • Cardiovirus Infections / immunology
  • Cardiovirus Infections / virology*
  • Cell Line
  • Central Nervous System / virology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Down-Regulation
  • Female
  • Mice
  • Molecular Sequence Data
  • RNA, Viral / biosynthesis
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription, Genetic
  • Viral Proteins / genetics
  • Viral Proteins / physiology*
  • Virulence
  • Virus Replication / physiology

Substances

  • Cytokines
  • RNA, Viral
  • Viral Proteins