title: Mumps Virus Is Released from the Apical Surface of Polarized Epithelial Cells, and the Release Is Facilitated by a Rab11-Mediated Transport System.
abstract: Mumps virus (MuV) is an airborne virus that causes a systemic infection in patients. In vivo, the epithelium is a major replication site of MuV, and thus, the mode of MuV infection of epithelial cells is a subject of interest. Our data in the present study showed that MuV entered polarized epithelial cells via both the apical and basolateral surfaces, while progeny viruses were predominantly released from the apical surface. In polarized cells, intracellular transport of viral ribonucleoprotein (vRNP) complexes was dependent on Rab11-positive endosomes, and vRNP complexes were transported to the apical membrane. Expression of a dominant negative form of Rab11 (Rab11S25N) reduced the progeny virus release in polarized cells but not in nonpolarized cells. Although in this way these effects were correlated with cell polarity, Rab11S25N did not modulate the direction of virus release from the apical surface. Therefore, our data suggested that Rab11 is not a regulator of selective apical release of MuV, although it acts as an activator of virus release from polarized epithelial cells. In addition, our data and previous studies on Sendai virus, respiratory syncytial virus, and measles virus suggested that selective apical release from epithelial cells is used by many paramyxoviruses, even though they cause either a systemic infection or a local respiratory infection.
  
  
  OBJECTIVE
  Mumps virus (MuV) is the etiological agent of mumps and causes a systemic infection. However, the precise mechanism by which MuV breaks through the epithelial barriers and achieves a systemic infection remains unclear. In the present study, we show that the entry of MuV is bipolar, while the release is predominantly from the apical surface in polarized epithelial cells. In addition, the release of progeny virus was facilitated by a Rab11-positive recycling endosome and microtubule network. Our data provide important insights into the mechanism of transmission and pathogenesis of MuV.
authors.affiliation: Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan kato0704@nih.go.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katoh
authors.affiliation: Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nakatsu
authors.affiliation: Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Sakata
authors.affiliation: Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Kidokoro
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D004285:Dogs; D011992:Endosomes / Q000378:metabolism / Q000821:virology*; D004847:Epithelial Cells / Q000821:virology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D009109:Mumps virus / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D057074:Virus Release / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D049452:Green Fluorescent Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C485184:enhanced green fluorescent protein