Abstract
Ovine rinderpest or goat plague is an economically important and contagious viral disease of sheep and goats, caused by the Peste des petits ruminants virus (PPRV). Differences in susceptibility to goat plague among different breeds and water buffalo exist. The host innate immune system discriminates between pathogen associated molecular patterns and self antigens through surveillance receptors known as Toll like receptors (TLR). We investigated the role of TLR and cytokines in differential susceptibility of goat breeds and water buffalo to PPRV. We examined the replication of PPRV in peripheral blood mononuclear cells (PBMC) of Indian domestic goats and water buffalo and demonstrated that the levels of TLR3 and TLR7 and downstream signalling molecules correlation with susceptibility vs resistance. Naturally susceptible goat breeds, Barbari and Tellichery, had dampened innate immune responses to PPRV and increased viral loads with lower basal expression levels of TLR 3/7. Upon stimulation of PBMC with synthetic TLR3 and TLR7 agonists or PPRV, the levels of proinflammatory cytokines were found to be significantly higher while immunosuppressive interleukin (IL) 10 levels were lower in PPRV resistant Kanni and Salem Black breeds and water buffalo at transcriptional level, correlating with reduced viralloads in infected PBMC. Water buffalo produced higher levels of interferon (IFN) α in comparison with goats at transcriptional and translational levels. Pre-treatment of Vero cells with human IFNα resulted in reduction of PPRV replication, confirming the role of IFNα in limiting PPRV replication. Treatment with IRS66, a TLR7 antagonist, resulted in the reduction of IFNα levels, with increased PPRV replication confirming the role of TLR7. Single nucleotide polymorphism analysis of TLR7 of these goat breeds did not show any marked nucleotide differences that might account for susceptibility vs resistance to PPRV. Analyzing other host genetic factors might provide further insights on susceptibility to PPRV and genetic polymorphisms in the host.
Highlights
Peste des petits ruminants (PPR), known as ovine rinderpest or goat plague, is an acute, highly contagious viral disease of goats and sheep, caused by the Peste des petits ruminants virus (PPRV), a morbillivirus in the family Paramyxoviridae
We examined the relative basal expression levels of TLR3 and TLR7 mRNA in naive peripheral blood mononuclear cells (PBMC) by quantitative real-time RT-PCR in nine individual animals per breed (n = 9)
The Kanni and Salem Black breeds revealed significantly higher basal TLR3 (p,0.001) and TLR7 (p,0.001) transcripts than Barbari goats while there were no significant difference (p.0.05) between Tellicherry and Barbari breeds (Figure 1). To understand their contribution to virus replication, PBMC from each of these four goat breeds (n = 5) were infected with 16103.0 mean tissue culture infective dose (TCID50) of PPRV and the virus load analyzed at 24 h post infection (PI) by quantitative real-time RT-PCR (qRT-PCR), using primers specific to the PPRV-H gene and TCID50
Summary
Peste des petits ruminants (PPR), known as ovine rinderpest or goat plague, is an acute, highly contagious viral disease of goats and sheep, caused by the Peste des petits ruminants virus (PPRV), a morbillivirus in the family Paramyxoviridae. PPRV infection results in great economic losses and affects productivity of sheep and goats subsequent to the global eradication of Rinderpest [2]. In 2004, the economic cost of PPRV in India was estimated to be 1800 million Indian rupees (US$ 39 million) per year [2,3]. PPRV replication and seroconversion has been demonstrated in large ruminants [4]. In September 2004, outbreaks of PPR in Sudan affected both sheep and camels [6]
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