Pathology Review of Two New Rift Valley Fever Virus Ruminant Models

Authors: DAVIS, SALLY - Kansas State University; Wilson, William - Bill; FABURAY, BONTO - Kansas State University; RICJT, JUERGEN - Kansas State University

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 10/20/2016
Publication Date: 10/20/2016
Citation: Davis, S.A., Wilson, W.C., Faburay, B., Ricjt, J.A. 2016. Pathology Review of Two New Rift Valley Fever Virus Ruminant Models. Meeting Abstract. 1.

Interpretive Summary: Rift Valley fever virus (RVFV), is a mosquito-borne, zoonotic pathogen within genus Phlebovirus, family Bunyaviridae that typically causes outbreaks in sub-Saharan Africa and recently spread to the Arabian Peninsula. In ruminants, RVFV infections cause mass abortion and high mortality rates in neonates. In humans, Rift Valley fever (RVF) often presents as an acute febrile illness but may progress to severe disease, including retinal vasculitis, encephalitis, hepatitis, hemorrhagic fever and death. There is no antiviral therapy. Both Europe and North America have experimentally competent RVFV vectors. However, they have no fully licensed vaccines for use in ruminants or humans. In endemic countries the standard veterinary control approach is vaccination with attenuated vaccines. However, these vaccines have the potential for teratogenicity as well as reversion to virulence or reassortment with RVFV field strains. They are not differentiating infected from vaccinated (DIVA) compliant and therefore unlikely to be approved for use during an epizootic in the US or Europe. The existence of naïve economically important ruminant populations in Europe and North America, the human disease risk and the potential to weaponize RVFV warrant a One Health approach to the development of vaccine and other control strategies. We developed sheep and cattle challenge models for RVF. These are unique in that they are subcutaneous inoculation models that reliably produce clinical disease in juevniles. We compared two genetically-distinct RVFV strains, Saudi Arabia 2001 and Kenya 2006 (Ken06). We demonstrated differences in viremia and clinico-pathological changes. Development of these challenge models and our more recent use of the Ken06 sheep model for vaccine efficacy testing afforded examination of RVFV pathology in multiple organs.

Technical Abstract: Rift Valley fever virus (RVFV), is a mosquito-borne, zoonotic pathogen within genus Phlebovirus, family Bunyaviridae that typically causes outbreaks in sub-Saharan Africa and recently spread to the Arabian Peninsula. In ruminants, RVFV infections cause mass abortion and high mortality rates in neonates. In humans, Rift Valley fever (RVF) often presents as an acute febrile illness but may progress to severe disease, including retinal vasculitis, encephalitis, hepatitis, hemorrhagic fever and death. There is no antiviral therapy. Both Europe and North America have experimentally competent RVFV vectors. However, they have no fully licensed vaccines for use in ruminants or humans. In endemic countries the standard veterinary control approach is vaccination with attenuated vaccines. However, these vaccines have the potential for teratogenicity as well as reversion to virulence or reassortment with RVFV field strains. They are not differentiating infected from vaccinated (DIVA) compliant and therefore unlikely to be approved for use during an epizootic in the US or Europe. The existence of naïve economically important ruminant populations in Europe and North America, the human disease risk and the potential to weaponize RVFV warrant a One Health approach to the development of vaccine and other control strategies. We developed sheep and cattle challenge models for RVF. These are unique in that they are subcutaneous inoculation models that reliably produce clinical disease in juevniles. We compared two genetically-distinct RVFV strains, Saudi Arabia 2001 and Kenya 2006 (Ken06). We demonstrated differences in viremia and clinico-pathological changes. Development of these challenge models and our more recent use of the Ken06 sheep model for vaccine efficacy testing afforded examination of RVFV pathology in multiple organs.