Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets

Nipah virus (NiV) is a highly lethal paramyxovirus that recently emerged as a causative agent of febrile encephalitis and severerespiratory disease in humans. The ferret model has emerged as the preferred small-animal model with which to study NiV disease,but much is still unknown about the viral determinants of NiV pathogenesis, including the contribution of the C protein inferrets. Additionally, studies have yet to examine the synergistic effects of the various P gene products on pathogenesis in animalmodels. Using recombinant NiVs (rNiVs), we examine the sole contribution of the NiV C protein and the combined contributionsof the C andWproteins in the ferret model of NiV pathogenesis. We show that an rNiV void of C expression resulted in100% mortality, though with limited respiratory disease, like our previously reported rNiV void ofWexpression; this finding isin stark contrast to the attenuated phenotype observed in previous hamster studies utilizing rNiVs void of C expression. We alsoobserved that an rNiV void of both C andWexpression resulted in limited respiratory disease; however, there was severe neurologicaldisease leading to 60% mortality, and the surviving ferrets demonstrated sequelae similar to those for human survivors ofNiV encephalitis.