title: The Nipah Virus Glycoproteins - their distribution in infected and transfected polarized epithelial cells and the identification of basolateral transport signals
title: Die Nipahvirus Glykoproteine - Ihre Verteilung in infizierten und transfizierten polarisierten Epithelzellen und die Identifizierung basolateraler Transportsignale
Creators: name: Weise, Carolin
Publisher: name: Philipps-Universität Marburg
Year: 2012
Subjects: Infektion
Proteintransport
Glycoproteins
Transfektion
Basolaterale Transportsignale
Glykoproteine
Transfection
Nipah virus
Biowissenschaften, Biologie
Viren
Epithelial cells
Basolateral transport
Infection
Nipahvirus
Polarisierte Epithelzellen

description: The highly pathogenic Nipah virus
      (NiV) is aerially transmitted and replicates initially in
      polarized epithelial cells of the respiratory tract.
      Subsequently NiV spreads systemically, with extensive
      endothelial involvement leading to vasculitis, which is
      mostly responsible for the clinical disease. In pigs and in
      about half of human infections symptomatic respiratory
      illness is also observed.(27, 87, 100, 119) It is assumed
      that the patients with symptomatic respiratory tract
      infections were responsible for human-to-human
      transmission.(87) Thus, NiV infection of the airway mucosa is
      relevant not only for primary NiV infection, serving as a
      portal of virus entry, but also for virus shedding and
      transmission to other hosts. Beside respiratory epithelia,
      epithelial cells in the kidney and bladder have been shown to
      be infected in vivo and are suggested to be important sites
      of release of progeny virions into the urine.(26, 91, 98,
      109, 162) The aim of this study was to elucidate the
      molecular mechanisms of NiV spread within epithelial cells,
      focusing on the roles of the two surface glycoproteins G and
      F. Preliminary analysis showed the both glycoproteins are
      expressed at the basolateral surface of polarized MDCK
      cells.(150) It is known that basolateral expression of viral
      gylcoproteins in polarized cells can mediate cell-to-cell
      fusion and therefore disruption of the epithelial barrier in
      vivo. In this study it could be shown that NiV infection of
      polarized MDCK cells leads to the formation of viral foci.
      The finding that both NiV glycoproteins are not only apically
      expressed but also at lateral membranes in infected cells
      adjacent to noninfected cells suggests that the infection
      spreads by cell-to-cell fusion. Supporting this idea
      basolateral targeting signals were identified in the
      cytoplasmic domains of both NiV glycoproteins. Tyrosine 525
      in the F protein is part of an endocytosis signal(151) and is
      also responsible for basolateral sorting. Surprisingly, a
      dityrosine motif at position 28/29 in the G protein was
      identified to mediate polarized targeting. A dileucine motif
      predicted to function as sorting signal is not involved.
      Mutation of the targeting signal in one of the NiV
      glycoproteins prevented the fusion of polarized cells,
      suggesting that basolateral or bipolar F and G expression
      facilitates the spread of NiV within epithelial cell
      monolayers, thereby contributing to efficient virus spread in
      mucosal surfaces in early and late phases of infection. To
      elucidate the molecular mechanisms of the basolateral
      transport colocalization and Yeast Two-Hybrid studies with
      adaptor protein (AP) complexes were performed. The results
      indicate that AP-1B seems to be involved in basolateral
      sorting of NiV F and AP-4 may play a role for polarized
      targeting of NiV G.
description: In dieser Arbeit konnte gezeigt
      werden, dass die NiV-Infektion von polarisierten
      Epithelzellen zur Ausbildung von Synzytien führt. Diese
      Fusion benachbarter Zellen wird durch die basolaterale
      Verteilung der fusogenen NiV-Glykoproteinkomplexe
      hervorgerufen. Die basolaterale Lokalisation der
      Glykoproteine wird über Tyrosin-motive in den
      zytoplasmatischen Domänen des F- und G-Proteins vermittelt.
      Werden diese Tyrosine mutiert, werden beide Glykoproteine
      apikal transportiert und vermitteln keine Zell-Zell-Fusion
      mehr. Obwohl diese Untersuchungen in MDCK-Zellen, einer
      immortalisierten Nierenepithelzelllinie, durchgeführt wurden,
      kann man ver-muten, dass auch in den polarisierten
      Epithelzellen des Respirationstraktes die basolaterale
      Verteilung des F- und G-Proteins die Zell-Zell-Fusion
      vermittelt. Dadurch wird die Barriere früh in der Infektion
      zerstört und ein Ausbreiten der Infektion in das
      subepitheliale Gewebe kann stattfinden.