title: Intracellular transport of the measles virus ribonucleoprotein complex is mediated by Rab11A-positive recycling endosomes and drives virus release from the apical membrane of polarized epithelial cells.
abstract: Many viruses use the host trafficking system at a variety of their replication steps. Measles virus (MV) possesses a nonsegmented negative-strand RNA genome that encodes three components of the ribonucleoprotein (RNP) complex (N, P, and L), two surface glycoproteins, a matrix protein, and two nonstructural proteins. A subset of immune cells and polarized epithelial cells are in vivo targets of MV, and MV is selectively released from the apical membrane of polarized epithelial cells. However, the molecular mechanisms for the apical release of MV remain largely unknown. In the present study, the localization and trafficking mechanisms of the RNP complex of MV were analyzed in detail using recombinant MVs expressing fluorescent protein-tagged L proteins. Live cell imaging analyses demonstrated that the MV RNP complex was transported in a manner dependent on the microtubule network and together with Rab11A-containing recycling endosomes. The RNP complex was accumulated at the apical membrane and the apical recycling compartment. The accumulation and shedding of infectious virions were severely impaired by expression of a dominant negative form of Rab11A. On the other hand, recycling endosome-mediated RNP transport was totally dispensable for virus production in nonpolarized cells. These data provide the first demonstration of the regulated intracellular trafficking events of the MV RNP complex that define the directional viral release from polarized epithelial cells.
authors: Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan. ynakatsu@nih.go.jp
authors: Yuichiro
authors: Y
authors: Nakatsu
authors: Xuemin
authors: X
authors: Ma
authors: Fumio
authors: F
authors: Seki
authors: Tadaki
authors: T
authors: Suzuki
authors: Masaharu
authors: M
authors: Iwasaki
authors: Yusuke
authors: Y
authors: Yanagi
authors: Katsuhiro
authors: K
authors: Komase
authors: Makoto
authors: M
authors: Takeda
mesh_terms: D000818:Animals; D019677:Artificial Gene Fusion; D001692:Biological Transport; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism*; D004847:Epithelial Cells / Q000821:virology*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D054884:Host-Pathogen Interactions; D006801:Humans; D008459:Measles virus / Q000502:physiology*; D012367:RNA, Viral / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics; D012261:Ribonucleoproteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism; D057074:Virus Release
chemical_list: D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D014764:Viral Proteins; D049452:Green Fluorescent Proteins