title: The microtubule motor protein KIF13A is involved in intracellular trafficking of the Lassa virus matrix protein Z.
abstract: The small matrix protein Z of arenaviruses has been identified as the main driving force to promote viral particle production at the plasma membrane. Although multiple functions of Z in the arenaviral life cycle have been uncovered, the mechanism of intracellular transport of Z to the site of virus budding is poorly understood and cellular motor proteins that mediate Z trafficking remain to be identified. In the present study, we report that the Z protein of the Old World arenavirus Lassa virus (LASV) interacts with the kinesin family member 13A (KIF13A), a plus-end-directed microtubule-dependent motor protein. Plasmid-driven overexpression of KIF13A results in relocalization of Z to the cell periphery, while functional blockage of endogenous KIF13A by overexpression of a dominant-negative mutant or KIF13A-specific siRNA causes a perinuclearaccumulation and decreased production of both Z-induced virus-like particles and infectious LASV. The interaction of KIF13A with Z proteins from both Old and New World arenaviruses suggests a conserved intracellular transport mechanism. In contrast, the intracellular distribution of the matrix proteins of prototypic members of the paramyxo- and rhabdovirus family is independent of KIF13A. In summary, our studies identify for the first time a molecular motor protein as a critical mediator for intracellular microtubule-dependent transport of arenavirus matrix proteins.
authors.affiliation: Institute of Virology, Philipps-University Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany.
authors.forename: Sarah Katharina
authors.initials: SK
authors.lastname: Fehling
authors.forename: Takeshi
authors.initials: T
authors.lastname: Noda
authors.forename: Andrea
authors.initials: A
authors.lastname: Maisner
authors.forename: Boris
authors.initials: B
authors.lastname: Lamp
authors.forename: Karl-Klaus
authors.initials: KK
authors.lastname: Conzelmann
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Klenk
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Garten
authors.forename: Thomas
authors.initials: T
authors.lastname: Strecker
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D002522:Chlorocebus aethiops; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000821:virology; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007836:Lassa virus / Q000502:physiology*; D008099:Liver / Q000473:pathology / Q000821:virology; D008870:Microtubules / Q000378:metabolism* / Q000821:virology; D011485:Protein Binding; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D014709:Vero Cells; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D057074:Virus Release / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; C417670:KIF13A protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D014763:Viral Matrix Proteins; C487631:protein Z, Lassa virus; D016547:Kinesins