title: Role of actin filaments in targeting of Crimean Congo hemorrhagic fever virus nucleocapsid protein to perinuclear regions of mammalian cells.
abstract: Crimean-Congo hemorrhagic fever virus is the causative agent of a severe disease throughout Africa, Europe, and Asia. Like other members of the genus Nairovirus, the Crimean-Congo hemorrhagic fever virus contains three genomic RNA segments, the small (S), medium (M), and large (L) segments. The S segment encodes the viral nucleocapsid protein (NP), while the M and L segments encode the glycoproteins and the RNA-dependent RNA polymerase, respectively. In this study, the site of expression and assembly of Crimean-Congo hemorrhagic fever virus NP in mammalian cells have been investigated. It was found that the NP is localized in the perinuclear region of infected cells. By using the Semliki forest virus expression system, it was shown that the Crimean-Congo hemorrhagic fever virus NP is targeted to the perinuclear region of cells in the absence of native RNA segments and virally encoded glycoproteins. It was also demonstrated that the Crimean-Congo hemorrhagic fever virus NP was not expressed as a Golgi-membrane associated protein. By using Cytochalasin D, an agent that disrupts actin filaments, it was found that actin filaments are involved in targeting the viral NP to perinuclear regions. We also demonstrated that disruption of actin filaments reduced the assembly of infectious Crimean-Congo hemorrhagic fever virus up to 97%. Furthermore, we showed that the NP of Crimean-Congo hemorrhagic fever virus NP interacts with actin.
authors.affiliation: Center for Microbiological Preparedness,Swedish Institute for Infectious Disease Control, SE Solna, Sweden.
authors.forename: Ida
authors.initials: I
authors.lastname: Andersson
authors.forename: Melinda
authors.initials: M
authors.lastname: Simon
authors.forename: Ake
authors.initials: A
authors.lastname: Lundkvist
authors.forename: Mikael
authors.initials: M
authors.lastname: Nilsson
authors.forename: Anna
authors.initials: A
authors.lastname: Holmström
authors.forename: Fredrik
authors.initials: F
authors.lastname: Elgh
authors.forename: Ali
authors.initials: A
authors.lastname: Mirazimi
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000502:physiology*; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000378:metabolism*; D012672:Semliki forest virus / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D019065:Virus Assembly
chemical_list: D019590:Nucleocapsid Proteins