|FABURAY, BONTO - Kansas State University|
|LIU, QINFANG - Kansas State University|
|DAVIS, A - Kansas State University|
|SHIVANNA, VINAY - Kansas State University|
|SUNWOO, SUN - Kansas State University|
|LANG, YUEKUN - Kansas State University|
|MOROZOV, IGOR - Kansas State University|
|MA, WENJUN - Kansas State University|
|RICHT, JUERGEN - Kansas State University|
Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/3/2015
Publication Date: 1/1/2016
Citation: Faburay, B., Gaudreault, N.N., Liu, Q., Davis, A.S., Shivanna, V., Sunwoo, S.Y., Lang, Y., Morozov, I., Ruder, M.G., Drolet, B.S., Mcvey, D.S., Ma, W., Wilson, W.C., Richt, J. 2016. Development of a sheep challenge model for Rift Valley fever. Virology. 489:128-140.
Interpretive Summary: This publication describes development of a model for direct viral challenge of sheep. This model represents a relevant large animal model for RVF vaccine studies. The major clinic-pathological features such as viremia, fever, hepatitis, hepatic necrosis are well reproduced in this host and could be further utilized to understand RVFV pathogenesis and RVFV-induced pathology. The two genetically distinct viruses (Ken06 and SA01) have distinct phenotypes observed in the associated clinical signs, with Ken06 manifesting higher virulence in the Dorper x Katahdin cross. The segment for both Ken06 and SA01 are nearly identical to ZH-501 (L 97.2-97.3%, M 96.6%, S 96.6-96.9%) but still are more closely related to each other (L 98.1%, M98.5%, 98.2%). These three strains do separate into distinct phylogenetic clades (data not shown). RVFV strains do appear to be changing with time but whether these changes are affecting virulence is uncertain. However, the severity of clinic-pathological features in the Polypay sheep suggests potential significant breed influence on the clinical and pathological outcome of RVFV infection. Future studies should be directed at understanding the susceptibility of different breeds of US sheep to RVFV infection.
Technical Abstract: Rift Valley fever is a zoonotic disease responsible for severe outbreaks in ruminant livestock characterized by mass abortion and high mortality rates in younger animals. The lack of a fully licensed vaccine in the US has spurred increased demand for a protective vaccine. Thus, development of a reliable challenge model is an important prerequisite for evaluation of existing and novel vaccines. A study was performed aimed at understanding the pathogenesis of Rift Valley fever virus (RVFV) infection in US sheep using two genetically different wild type strains of the virus, Saudi Arabia 2001 (SA01) and Kenya 2006 (Ken06). A group of sheep, Dorper x Katahdin cross, was challenged subcutaneously with 1 x 106 PFU of either the SA01 or Ken06 strain. Additionally, another group of sheep, Polypay breed, was similarly challenged with a higher dose of Ken06 strain. Challenged animals manifested early-onset viremia accompanied by transient increase in rectal temperatures. Sheep seroconverted and showed time-dependent increase in virus neutralizing antibody titers in response to the virulent inoculation. The Ken06 strain manifested higher virulence by inducing higher liver enzyme levels, as well as more severe liver pathologies compared to the SA01 strain. The histopathological responses to virulent challenge were characterized by hepatocellular degeneration and necrosis, neutrophil and macrophage infiltration at the necrotic foci. Hepatocytes in affected liver also exhibited strong positive staining for RVFV antigen.