title: The C-terminal domain of chikungunya virus nsP2 independently governs viral RNA replication, cytopathicity, and inhibition of interferon signaling.
abstract: Alphavirus nonstructural protein 2 (nsP2) has pivotal roles in viral RNA replication, host cell shutoff, and inhibition of antiviral responses. Mutations that individually rendered other alphaviruses noncytopathic were introduced into chikungunya virus nsP2. Results show that (i) nsP2 mutation P718S only in combination with KR649AA or adaptive mutation D711G allowed noncytopathic replicon RNA replication, (ii) prohibiting nsP2 nuclear localization abrogates inhibition of antiviral interferon-induced JAK-STAT signaling, and (iii) nsP2 independently affects RNA replication, cytopathicity, and JAK-STAT signaling.
authors.affiliation: Laboratory of Virology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Jelke J
authors.initials: JJ
authors.lastname: Fros
authors.forename: Erika
authors.initials: E
authors.lastname: van der Maten
authors.forename: Just M
authors.initials: JM
authors.lastname: Vlak
authors.forename: Gorben P
authors.initials: GP
authors.lastname: Pijlman
mesh_terms: D000818:Animals; D002646:Chikungunya virus / Q000472:pathogenicity / Q000502:physiology*; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral; D007372:Interferons / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D017361:Viral Nonstructural Proteins; D007372:Interferons