title: Viral protein determinants of Lassa virus entry and release from polarized epithelial cells.
abstract: The epithelium plays a key role in the spread of Lassa virus. Transmission from rodents to humans occurs mainly via inhalation or ingestion of droplets, dust, or food contaminated with rodent urine. Here, we investigated Lassa virus infection in cultured epithelial cells and subsequent release of progeny viruses. We show that Lassa virus enters polarized Madin-Darby canine kidney (MDCK) cells mainly via the basolateral route, consistent with the basolateral localization of the cellular Lassa virus receptor alpha-dystroglycan. In contrast, progeny virus was efficiently released from the apical cell surface. Further, we determined the roles of the glycoprotein, matrix protein, and nucleoprotein in directed release of nascent virus. To do this, a virus-like-particle assay was developed in polarized MDCK cells based on the finding that, when expressed individually, both the glycoprotein GP and matrix protein Z form virus-like particles. We show that GP determines the apical release of Lassa virus from epithelial cells, presumably by recruiting the matrix protein Z to the site of virus assembly, which is in turn essential for nucleocapsid incorporation into virions.
authors.affiliation: Institute of Virology, Philipps University Marburg, Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schlie
authors.forename: Anna
authors.initials: A
authors.lastname: Maisa
authors.forename: Fabian
authors.initials: F
authors.lastname: Freiberg
authors.forename: Allison
authors.initials: A
authors.lastname: Groseth
authors.forename: Thomas
authors.initials: T
authors.lastname: Strecker
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Garten
mesh_terms: D000818:Animals; D016466:CHO Cells; D016764:Cell Polarity; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004847:Epithelial Cells / Q000821:virology*; D006023:Glycoproteins / Q000032:analysis / Q000502:physiology; D006801:Humans; D007836:Lassa virus / Q000502:physiology*; D009698:Nucleoproteins / Q000032:analysis / Q000502:physiology; D014763:Viral Matrix Proteins / Q000032:analysis / Q000502:physiology; D014764:Viral Proteins / Q000502:physiology*; D014771:Virion / Q000502:physiology; D053586:Virus Internalization
chemical_list: D006023:Glycoproteins; D009698:Nucleoproteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins