Pathogenesis of peste des petits ruminants virus in experimentally infected sheep.

Peste des petits ruminants virus (PPRV) is a highly contagious morbillivirus affecting small ruminants. PPRV infection leads to a range of clinical signs, including fever, respiratory distress and diarrhoea. Infection of myeloid and lymphoid cells causes immune suppression, resulting in increased susceptibility to opportunistic infections. Higher disease severity is reported in goats as compared to sheep, but comparative pathogenesis studies of PPRV in these species are limited. We recently performed experimental PPRV infections in goats and now used the same strains and routes of inoculation for a pathogenesis study in sheep. Animals were inoculated with either the low virulent strain Cote d'Ivoire/1989 (PPRV/IvoryCoast) or the more virulent recombinant rPPRV/Georgia/Tbilisi/2016 modified to express enhanced green fluorescent protein (rPPRV/Tbilisi-EGFP). Clinical signs were mild or absent, and levels of lymphopenia, viremia and virus shedding were lower than those observed in goats, but all animals seroconverted. Macroscopic fluorescence was detected in lymphoid tissues, airways, skin, mucosae and intestines of animals infected with rPPRV/Tbilisi-EGFP. Immunohistochemistry identified infected B-and T-cells in lymphoid tissues, as well as infection of epithelial cells in the skin and mucosae, leading to degeneration and necrosis. Infection levels were substantially lower in animals inoculated with PPRV/IvoryCoast, but infected cell types were similar. Taken together, experimental PPRV infection of sheep resulted in mild disease but detectable virus replication, with comparable phenotypes of infected tissues and cells as previously observed in goats. These data support the hypothesis that severity of PPRV disease in small ruminants is mediated by opportunistic infections following viral immune suppression.