title: The immunomodulating V and W proteins of Nipah virus determine disease course.
abstract: The viral determinants that contribute to Nipah virus (NiV)-mediated disease are poorly understood compared with other paramyxoviruses. Here we use recombinant NiVs (rNiVs) to examine the contributions of the NiV V and W proteins to NiV pathogenesis in a ferret model. We show that a V-deficient rNiV is susceptible to the innate immune response in vitro and behaves as a replicating non-lethal virus in vivo. Remarkably, rNiV lacking W expression results in a delayed and altered disease course with decreased respiratory disease and increased terminal neurological disease associated with altered in vitro inflammatory cytokine production. This study confirms the V protein as the major determinant of pathogenesis, also being the first in vivo study to show that the W protein modulates the inflammatory host immune response in a manner that determines the disease course.
authors.affiliation: 1] Galveston National Laboratory, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA [2] Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Satterfield
authors.affiliation: 1] Galveston National Laboratory, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA [2] Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Cross
authors.affiliation: 1] Galveston National Laboratory, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA [2] Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA.
authors.forename: Karla A
authors.initials: KA
authors.lastname: Fenton
authors.affiliation: 1] Galveston National Laboratory, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA [2] Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA.
authors.forename: Krystle N
authors.initials: KN
authors.lastname: Agans
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Basler
authors.affiliation: 1] Galveston National Laboratory, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA [2] Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
authors.affiliation: 1] Galveston National Laboratory, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA [2] Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA.
authors.forename: Chad E
authors.initials: CE
authors.lastname: Mire
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D018925:Chemokines / Q000276:immunology*; D006224:Cricetinae; D016207:Cytokines / Q000276:immunology; D018450:Disease Progression; D042783:Endothelial Cells / Q000276:immunology / Q000821:virology; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D005289:Ferrets; D045464:Henipavirus Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D066298:In Vitro Techniques; D045405:Nipah Virus / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology*; D019562:Viral Load; D014764:Viral Proteins / Q000276:immunology*; D015678:Viral Structural Proteins / Q000276:immunology*
chemical_list: D018925:Chemokines; D016207:Cytokines; D010750:Phosphoproteins; C539757:V protein, Nipah virus; D014764:Viral Proteins; D015678:Viral Structural Proteins; C501252:W protein, Nipah virus