Differential IFN-alpha/beta production suppressing capacities of the leader proteins of mengovirus and foot-and-mouth disease virus.
Picornaviruses encompass a large family of RNA viruses. Some picornaviruses possess a leader (L) protein at the N-terminus of their polyprotein. The L proteins of encephalomyocarditis virus, a cardiovirus, and foot-and-mouth disease virus (FMDV), an aphthovirus, are both dispensable for replication and their major function seems to be the suppression of antiviral host cell responses. Previously, we showed that the L protein of mengovirus, a strain of encephalomyocarditis virus, inhibits antiviral responses by inhibiting type I interferon (IFN-alpha/beta) gene transcription. The L protein of the FMDV is a protease (L(pro)) that cleaves cellular factors to reduce cytokine and chemokine mRNA production and to inhibit cap-dependent cellular host mRNA translation, thereby limiting the production of proteins with antiviral activity. In this study, we constructed a viable chimeric mengovirus that expresses FMDV L(pro) in place of the authentic L protein in order to compare the efficiency of the immune evasion mechanisms mediated by L and L(pro) respectively. We show that in this mengovirus background the L protein is more potent than FMDV L(pro) in suppressing IFN-alpha/beta responses. Yet, FMDV L(pro) is important to antagonize infection-limiting responses both in vitro and in vivo.
Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
Stanleyson V
SV
Hato
Frédéric
F
Sorgeloos
Celine
C
Ricour
January
J
Zoll
Willem J G
WJ
Melchers
Thomas
T
Michiels
Frank J M
FJ
van Kuppeveld
D000818:Animals; D018188:Cardiovirus Infections / Q000473:pathology / Q000821:virology; D002460:Cell Line; D006224:Cricetinae; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity*; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000276:immunology*; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000276:immunology*; D008574:Mengovirus / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity*; D051379:Mice; D011995:Recombination, Genetic; D016019:Survival Analysis; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology
D016898:Interferon-alpha; D014764:Viral Proteins; D037521:Virulence Factors; D016899:Interferon-beta