African Horse Sickness virus: pathogenicity in an IFNAR(-/-) mouse model of infection

Abstract

African Horse Sickness (AHS) is a highly lethal, vector-borne viral disease of equids, endemic to sub-Saharan Africa but with a history of outbreaks into Europe. The pathogenesis of the virus is not fully understood; some studies have shown that certain proteins are linked to virulence, and that the outcome of infection is highly dependent on viral factors. Disease can also manifest with several different presentations in the equine host (fever form, cardiac form, pulmonary form and mixed form) but the mechanism underlying this variation is not fully understood. Pathogenicity and virulence studies of AHSV are difficult to perform in horses for logistical, ethical and financial reasons. As an alternative, Interferon-alpha receptor knockout (IFNAR-/-) mice have previously been used in AHSV vaccinology studies. Full pathology characterization of the AHSV infection in this model is the primary objective of our work, which will address questions regarding pathogenesis of AHSV. Here we present data collected from experimental infection of IFNAR (-/-) mice with a strain of AHSV serotype 4, including: clinical signs; histopathology; immuno-histochemical analysis of immune response to infection; antigen detection in tissues; and transmission electron microscopy of AHSV infected tissues. In addition, we will show data from experimental infection in this animal model comparing the pathogenicity of different AHSV strains. Results obtained indicate AHSV-4 infection is correlated with oedema and pneumonia in the lungs, inflammation in the liver and meningitis plus perivascular cuffing in the cerebrum. Other data shows that different strains of AHSV differ in terms of their pathogenicity and tropism.