title: Human MxA protein inhibits the replication of Crimean-Congo hemorrhagic fever virus.
abstract: Crimean-Congo hemorrhagic fever virus (CCHFV) belongs to the genus Nairovirus within the family Bunyaviridae and is the causative agent of severe hemorrhagic fever. Despite increasing knowledge about hemorrhagic fever viruses, the factors determining their pathogenicity are still poorly understood. The interferon-induced MxA protein has been shown to have an inhibitory effect on several members of the Bunyaviridae family, but the effect of MxA against CCHFV has not previously been studied. Here, we report that human MxA has antiviral activity against CCHFV. The yield of progeny virus in cells constitutively expressing MxA was reduced up to 1,000-fold compared with control cells, and accumulation of viral genomes was blocked. Confocal microscopy revealed that MxA colocalizes with the nucleocapsid protein (NP) of CCHFV in the perinuclear regions of infected cells. Furthermore, we found that MxA interacted with NP by using a coimmunoprecipitation assay. We also found that an amino acid substitution (E645R) within the C-terminal domain of MxA resulted in a loss of MxA antiviral activity and, concomitantly, in the capacity to interact with CCHFV NP. These results suggest that MxA, by interacting with a component of the nucleocapsid, prevents replication of CCHFV viral RNA and thereby inhibits the production of new infectious virus particles.
authors.affiliation: Center for Microbiological Preparedness/Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
authors.forename: Ida
authors.initials: I
authors.lastname: Andersson
authors.forename: Linda
authors.initials: L
authors.lastname: Bladh
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Mousavi-Jazi
authors.forename: Karl-Eric
authors.initials: KE
authors.lastname: Magnusson
authors.forename: Ake
authors.initials: A
authors.lastname: Lundkvist
authors.forename: Otto
authors.initials: O
authors.lastname: Haller
authors.forename: Ali
authors.initials: A
authors.lastname: Mirazimi
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism; D001483:Base Sequence; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D064547:Myxovirus Resistance Proteins; D019590:Nucleocapsid Proteins / Q000502:physiology; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014709:Vero Cells; D014774:Virulence; D014779:Virus Replication / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D019590:Nucleocapsid Proteins; D012367:RNA, Viral; D011994:Recombinant Proteins; D019204:GTP-Binding Proteins