Modeling PPRV pathogenesis in mice to assess the contribution of innate cells and anti-viral T cells

2020 
We demonstrate a rapid induction of type I IFN response in PPRV stimulated cells and the susceptibility of mice, genetically ablated of interferon response, to PPRV infection. Following PPRV infection, IFNR KO mice gradually reduced their body weights and succumbed to the infection within 10 days. While the infecting inoculum size did not alter the outcome of infection, the nature of the induced disease was qualitatively different. Immunopathological lesions were characterized by the expansion and infiltration of innate immune cells distinctly evident at the lower infecting dose of PPRV infection. The replicating virus particles as well as the viral antigens were abundant in most of the critical organs of PPRV infected IFNR KO mice. Neutrophils and macrophages transported the replicating virus to central nervous system and contributed to pathology while the NK cells and T cells were protective against the virus. Using an array of fluorescently labeled H-2Kb tetramers PPRV specific CD8+ T cells responses were identified and measured in the infected as well as the peptide immunized mice. Our study therefore established and employed a laboratory animal model for investigating PPRV pathogenesis and the contribution of virus specific CD8+ T cells during the virus infection to pave the way for elucidating protective or pathological roles of immune cells during PPRV infection. ImportanceWe developed a laboratory animal model for investigating the pathogenesis and immunity induced by PPRV. IFNR KO animals succumbed to the infection irrespective of the dose and the route of infection. Neutrophils and macrophages served as the Trojan horse and helped transport the virus to CNS to cause encephalitis while the NK cells and CD8+ T cells provided the protection against PPRV infection. We additionally identified class I restricted immunogenic epitopes of PPRV in C57BL/6 mice. Our study therefore paves the way for an optimal utilization of this model to unravel PPRV pathogenesis and assessing the host correlates of protection.
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