The immunomodulating V and W proteins of Nipah virus determine disease course

• Published in: Nature communications Vol. 6; no. 1; p. 7483
• Main Authors: Satterfield, Benjamin A., Cross, Robert W., Fenton, Karla A., Agans, Krystle N., Basler, Christopher F., Geisbert, Thomas W., Mire, Chad E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.06.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 13/106; 13/109; 13/51; 631/250/256; 631/326/596/2553; 631/326/596/2555; 692/699/255/2514; Animals; Blotting, Western; Cell Line; Chemokines - immunology; Cricetinae; Cytokines - immunology; Disease Progression; Endothelial Cells - immunology; Endothelial Cells - virology; Epithelial Cells - immunology; Epithelial Cells - virology; Ferrets; Henipavirus Infections - immunology; Henipavirus Infections - virology; Humanities and Social Sciences; Humans; Immune response; Immunity, Innate - immunology; In Vitro Techniques; multidisciplinary; Nipah Virus - immunology; Phosphoproteins - immunology; Respiratory diseases; Science; Science (multidisciplinary); Viral Load; Viral Proteins - immunology; Viral Structural Proteins - immunology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms8483

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. Nipah virus (NiV) can be transmitted from bats and other animals to humans, causing severe encephalitis and respiratory disease. Here, Satterfield et al. show that the W protein of NiV modulates the host immune response and determines disease course in a ferret model of infection.