title: Nipah Virus Matrix Protein Influences Fusogenicity and Is Essential for Particle Infectivity and Stability.
abstract: Nipah virus (NiV) causes fatal encephalitic infections in humans. To characterize the role of the matrix (M) protein in the viral life cycle, we generated a reverse genetics system based on NiV strain Malaysia. Using an enhanced green fluorescent protein (eGFP)-expressing M protein-deleted NiV, we observed a slightly increased cell-cell fusion, slow replication kinetics, and significantly reduced peak titers compared to the parental virus. While increased amounts of viral proteins were found in the supernatant of cells infected with M-deleted NiV, the infectivity-to-particle ratio was more than 100-fold reduced, and the particles were less thermostable and of more irregular morphology. Taken together, our data demonstrate that the M protein is not absolutely required for the production of cell-free NiV but is necessary for proper assembly and release of stable infectious NiV particles.
  
  
  OBJECTIVE
  Henipaviruses cause a severe disease with high mortality in human patients. Therefore, these viruses can be studied only in biosafety level 4 (BSL-4) laboratories, making it more challenging to characterize their life cycle. Here we investigated the role of the Nipah virus matrix protein in virus-mediated cell-cell fusion and in the formation and release of newly produced particles. We found that even though low levels of infectious viruses are produced in the absence of the matrix protein, it is required for the release of highly infectious and stable particles. Fusogenicity of matrixless viruses was slightly enhanced, further demonstrating the critical role of this protein in different steps of Nipah virus spread.
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Dietzel
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany.
authors.forename: Larissa
authors.initials: L
authors.lastname: Kolesnikova
authors.affiliation: INRS-Institut Armand-Frappier, University of Quebec, Laval, Quebec, Canada Veterinary Medicine Division, Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: Bevan
authors.initials: B
authors.lastname: Sawatsky
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Heiner
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Weis
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany German Center for Infection Research, Partner Site Giessen-Marburg-Langen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Becker
authors.affiliation: INRS-Institut Armand-Frappier, University of Quebec, Laval, Quebec, Canada Veterinary Medicine Division, Paul-Ehrlich-Institut, Langen, Germany German Center for Infection Research, Partner Site Giessen-Marburg-Langen, Germany.
authors.forename: Veronika
authors.initials: V
authors.lastname: von Messling
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany maisner@staff.uni-marburg.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Maisner
mesh_terms: D000818:Animals; D002460:Cell Line; D017353:Gene Deletion; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D045405:Nipah Virus / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects / Q000648:ultrastructure; D059386:Reverse Genetics; D013696:Temperature; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000648:ultrastructure; D019065:Virus Assembly; D014776:Virus Cultivation; D057074:Virus Release; D014779:Virus Replication
chemical_list: D014763:Viral Matrix Proteins