Pathogenesis, Immune Evasion, and Host Genetic Susceptibility of Peste des Petits Ruminants Virus in Nigerian Indigenous Small Ruminants: An Original Mechanistic Analysis

This dissertation provides an original mechanistic analysis of PPR virus (PPRV) pathogenesis, immune evasion strategies, and host genetic susceptibility determinants in Nigerian indigenous small ruminant breeds, addressing a foundational knowledge gap in understanding why PPR causes variable disease severity in different Nigerian sheep and goat breeds and populations. Peste des Petits Ruminants causes massive mortality in susceptible small ruminant populations across West Africa, but the molecular basis for differential susceptibility between breeds and the mechanisms by which the Nigerian PPRV strains evade host immunity are uncharacterised. The dissertation employs a four-phase experimental design: PPRV strain isolation and full genome sequencing from outbreaks across the North East, North West, and North Central zones; experimental infection of three indigenous Nigerian sheep breeds (Uda, Yankasa, and West African Dwarf) and two goat breeds (Red Sokoto and West African Dwarf); in vitro mechanistic studies of viral RNA polymerase complex inhibition of innate immune signalling using cell lines derived from indigenous and exotic breeds; and genome-wide association studies in 400 indigenous animals genotyped with the OvineHD SNP array to identify host genetic loci associated with survival in experimentally challenged animals. The dissertation proposes the PPRV-Host Susceptibility Interaction Model (PHSIM) as an original theoretical contribution. Findings reveal that Uda sheep demonstrate significantly superior innate immune activation, with IFN-beta induction occurring 12 hours earlier than in Yankasa animals following experimental infection. Keywords: PPR virus, pathogenesis, immune evasion, genetic susceptibility, Nigerian small ruminants.