Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets
Authors: Jessica Graber
Benjamin A Satterfield
Christopher F Basler
Robert W Cross
Chad E Mire
Viktoriya Borisevich
Thomas W Geisbert
Karla A Fenton
Krystle N Agans
Daniel J Deer
Journal: Journal of virology (2016)
Discipline: MICROBIOLOGY
Keywords: Nipah virus; pathogenesis; ferret model; C protein; W protein
Affiliations: Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA., Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA., Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA., Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA .

Abstract:  Nipah virus (NiV) is a highly lethal paramyxovirus that recently emerged as a causative agent of febrile encephalitis and severe respiratory 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 in ferrets. Additionally, studies have yet to examine the synergistic effects of the various P gene products on pathogenesis in animal models. Using recombinant NiVs (rNiVs), we examine the sole contribution of the NiV C protein and the combined contributions of the C and W proteins in the ferret model of NiV pathogenesis. We show that an rNiV void of C expression resulted in 100% mortality, though with limited respiratory disease, like our previously reported rNiV void of W expression; this finding is in stark contrast to the attenuated phenotype observed in previous hamster studies utilizing rNiVs void of C expression. We also observed that an rNiV void of both C and W expression resulted in limited respiratory disease; however, there was severe neurological disease leading to 60% mortality, and the surviving ferrets demonstrated sequelae similar to those for human survivors of NiV encephalitis. Importance: Nipah virus (NiV) is a human pathogen capable of causing lethal respiratory and neurological disease. Many human survivors have long-lasting neurological impairment. Using a ferret model, this study demonstrated the roles of the NiV C and W proteins in pathogenesis, where lack of either the C or the W protein independently decreased the severity of clinical respiratory disease but did not decrease lethality. Abolishing both C and W expression, however, dramatically decreased the severity of respiratory disease and the level of destruction of splenic germinal centers. These ferrets still suffered severe neurological disease: 60% succumbed to disease, and the survivors experienced long-term neurological impairment, such as that seen in human survivors. This new ferret NiV C and W knockout model may allow, for the first time, the examination of interventions to prevent or mitigate the neurological damage and sequelae experienced by human survivors. 

Retracted: No

PubPeer comments:
 In Figure 8, images K and O appear to partially overlap, if flipped as illustrated. *** ![file] *** Full figure ![file] , 
 #1 Thank you for bringing this to our attention. We no longer have all of the original individual images and we are unsure exactly what happened, but it appears that the two H E photos mentioned were put as place holders and also represented the lesions (or lack thereof) that we were wanting to display so they unfortunately were overlooked in the final edits and were not exchanged for the actual photos. The results and conclusions were not altered with this mistake. In any case, we still have the original pathology H E and IHC slides and have taken new paired photos and will replace the original photos in an erratum submitted to the journal in order to avoid any confusion. , 
 Figure placeholders are a usually bad idea for many reasons. Especially when they are not labelled as such and rotated cropped to look even less like placeholders. I just believe using them is asking for troubles. ,