Toll-Like Receptor Responses to Peste des petits ruminants Virus in Goats and Water Buffalo

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.

RNAseq Reveals the Contribution of Interferon Stimulated Genes to the Increased Host Defense and Decreased PPR Viral Replication in Cattle

“…In contrast, immunosuppressive interleukin (IL) 10 levels were lower in PPR-resistant Kanni and Salem Black breeds of goat and water buffalo at the transcriptional level, correlating with reduced viral loads in infected PBMC. In addition, water buffalo also produced higher levels of interferon alpha (IFNα) in comparison with goats both at transcriptional and translational levels which were confirmed to be TLR7 mediated through inhibitor and pre-treatment studies [17]. Thus, differential gene expression analysis can be a very powerful first attempt to correlate immune responses with gene regulation.…”

“…The replication of PPRV in the PBMC of Indian domestic goats and water buffalo is influenced by the expression levels of TLR3, TLR7 and downstream signaling molecules. Upon stimulation of PBMC with synthetic TLR3 and TLR7 agonists or PPRV, the levels of pro-inflammatory cytokines were found to be significantly different across goats and water buffalo, a likely mechanism influencing differential susceptibility to disease [17]. In contrast, immunosuppressive interleukin (IL) 10 levels were lower in PPR-resistant Kanni and Salem Black breeds of goat and water buffalo at the transcriptional level, correlating with reduced viral loads in infected PBMC.…”

Immune gene variability influences roe deer natal dispersal

“…Variability in TLR3 expression may play an important role in disease susceptibility of white‐tailed deer to bluetongue and epizootic hemorrhagic disease viruses (Vos et al ). TLR3 is also involved in the susceptibility or resistance to ‘Peste des petits ruminants’ viral infection, which is responsible for the ovine rinderpest or goat plague (Dhanasekaran et al ). Finally, TLR5 is known to bind bacterial flagellin and is important in host defense against bacterial pathogens in several mammalian species (Metcalfe et al ).…”

Systems Perspective of Morbillivirus Replication

“…A breed effect on susceptibility/resistance to PPRV has also been reported [Lefevre and Diallo, 1990]. Although comprehensive information about all the host factors is lacking, one of the elements that has been identified and which makes water buffalo resistant to PPR (compared to goats) is the higher basal level expression of Toll-like receptors 3/7 [Dhanasekaran et al, 2014]. Systems virology can unravel all the host factors that may be responsible for disease resistance, like those identified for chicken flocks, differently susceptible for necrotic enteritis [Kim et al, 2014].…”