Abstract
The study was aimed at developing an accessible laboratory animal model to elucidate protective and pathological roles of immune mediators during Peste des petits ruminants virus (PPRV) infection. It is because of the critical roles of type I IFNs in anti-viral defense, we assessed the susceptibility of IFN receptor knock out (IFNR KO) mice to PPRV infection. IFNR KO mice were exceedingly susceptible to the infection but WT animals efficiently controlled PPRV. Accordingly, the PPRV infected IFNR KO mice gradually reduced their body weights and succumbed to the infection within 10 days irrespective of the dose and route of infection. The lower infecting doses predominantly induced immunopathological lesions. The viral antigens as well as the replicating PPRV were abundantly present in most of the critical organs such as brain, lungs, heart and kidneys of IFNR KO mice infected with high dose of the virus. Neutrophils and macrophages transported the replicating virus to central nervous system (CNS) and contributed to pathology while the elevated NK and T cell responses directly correlated with the resolution of PPRV infection in WT animals. Using an array of fluorescently labeled H-2Kb tetramers, we discovered four immunogenic epitopes of PPRV. The PPRV-peptides interacted well with H-2Kb in acellular and cellular assay as well as expanded the virus-specific CD8+ T cells in immunized or infected mice. Adoptively transferred CD8+ T cells helped control PPRV in infected mice. Our study therefore established and employed a mouse model for investigating the pathogenesis of PPRV. The model could be useful for elucidating the contribution of immune cells in disease progression as well as to test anti-viral agents.
Highlights
Peste des petits ruminants virus (PPRV) causes high mortality in herds of small ruminants and is responsible for major economic losses to livestock sector in developing countries [1,2,3,4]
We studied viral pathogenesis in mice ablated of IFN response and observed enhanced susceptibility of IFN receptor knockout (IFNR KO) mice to PPRV infection
Different doses of PPRV (1, 102,103 or 104 plaque forming units (PFU)) were i.p. inoculated into IFN receptor knock out (IFNR KO) mice and the disease progression was monitored up to eight dpi (Figure 1A)
Summary
Peste des petits ruminants virus (PPRV) causes high mortality in herds of small ruminants and is responsible for major economic losses to livestock sector in developing countries [1,2,3,4]. PPRV is a negative sense, single stranded enveloped virus of paramyxoviridae family that harbors several other members able to cause debilitating disease in animals and humans. The protective and pathological mechanisms activated by PPRV as well as the contribution of immune cells in the viral pathogenesis have not been adequately investigated. This could primarily be attributed to the unavailability of an accessible laboratory animal model. We, addressed this issue in the current investigation to develop a more accessible laboratory animal model to better understand immunity and immunopathology following PPRV infection
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