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Toll-like receptor responses to Peste des petits ruminants virus in goats and water buffalo.

Dhanasekaran S, Biswas M, Vignesh AR, Ramya R, Raj GD, Tirumurugaan KG, Raja A, Kataria RS, Parida S, Elankumaran S, Subbiah E - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai, Tamil Nadu, India.

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.

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PPRV replication in goat and buffalo PBMC.Buffalo PBMC were less permissive to PPRV replication as observed by the significantly higher PPRV viral loads (P<0.001) in PBMC of goat as compared to buffalo PBMC. A) Significantly higher PPRV H gene mRNA levels and B) Significantly higher viral load in goat as compared to buffalo PBMC.
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pone-0111609-g003: PPRV replication in goat and buffalo PBMC.Buffalo PBMC were less permissive to PPRV replication as observed by the significantly higher PPRV viral loads (P<0.001) in PBMC of goat as compared to buffalo PBMC. A) Significantly higher PPRV H gene mRNA levels and B) Significantly higher viral load in goat as compared to buffalo PBMC.

Mentions: In order to investigate the species specific disease outcome, we compared the permissiveness of goat or buffalo PBMC’s to PPRV replication invitro. Water buffalo supported significantly lower (about 4.89 fold) replication of PPRV than goat PBMC (p<0.001). Approximately 2 log10 difference in the virus yield was evident between buffalo and goat PBMC upon PPRV infection (Figure 3A & B).


Toll-like receptor responses to Peste des petits ruminants virus in goats and water buffalo.

Dhanasekaran S, Biswas M, Vignesh AR, Ramya R, Raj GD, Tirumurugaan KG, Raja A, Kataria RS, Parida S, Elankumaran S, Subbiah E - PLoS ONE (2014)

PPRV replication in goat and buffalo PBMC.Buffalo PBMC were less permissive to PPRV replication as observed by the significantly higher PPRV viral loads (P<0.001) in PBMC of goat as compared to buffalo PBMC. A) Significantly higher PPRV H gene mRNA levels and B) Significantly higher viral load in goat as compared to buffalo PBMC.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219731&req=5

pone-0111609-g003: PPRV replication in goat and buffalo PBMC.Buffalo PBMC were less permissive to PPRV replication as observed by the significantly higher PPRV viral loads (P<0.001) in PBMC of goat as compared to buffalo PBMC. A) Significantly higher PPRV H gene mRNA levels and B) Significantly higher viral load in goat as compared to buffalo PBMC.
Mentions: In order to investigate the species specific disease outcome, we compared the permissiveness of goat or buffalo PBMC’s to PPRV replication invitro. Water buffalo supported significantly lower (about 4.89 fold) replication of PPRV than goat PBMC (p<0.001). Approximately 2 log10 difference in the virus yield was evident between buffalo and goat PBMC upon PPRV infection (Figure 3A & B).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai, Tamil Nadu, India.

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.

Show MeSH
Related in: MedlinePlus