title: 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.
authors.affiliation: Department of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai, Tamil Nadu, India.
authors.forename: Sakthivel
authors.initials: S
authors.lastname: Dhanasekaran
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America.
authors.forename: Moanaro
authors.initials: M
authors.lastname: Biswas
authors.affiliation: Department of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai, Tamil Nadu, India.
authors.forename: Ambothi R
authors.initials: AR
authors.lastname: Vignesh
authors.affiliation: Department of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai, Tamil Nadu, India.
authors.forename: R
authors.initials: R
authors.lastname: Ramya
authors.affiliation: Department of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai, Tamil Nadu, India.
authors.forename: Gopal Dhinakar
authors.initials: GD
authors.lastname: Raj
authors.affiliation: Department of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai, Tamil Nadu, India.
authors.forename: Krishnaswamy G
authors.initials: KG
authors.lastname: Tirumurugaan
authors.affiliation: Department of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai, Tamil Nadu, India.
authors.forename: Angamuthu
authors.initials: A
authors.lastname: Raja
authors.affiliation: Animal Genetics Division, National Bureau of Animal Genetic Resources, Karnal (Haryana), India.
authors.forename: Ranjit S
authors.initials: RS
authors.lastname: Kataria
authors.affiliation: Head of FMD Vaccine Differentiation Group, The Pirbright Institute, Surrey, United Kingdom.
authors.forename: Satya
authors.initials: S
authors.lastname: Parida
authors.forename: Subbiah
authors.initials: S
authors.lastname: Elankumaran
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America.
authors.forename: Elankumaran
authors.initials: E
authors.lastname: Subbiah
mesh_terms: D000818:Animals; D002020:Buffaloes / Q000276:immunology / Q000821:virology*; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006041:Goats / Q000235:genetics / Q000276:immunology / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate; D029021:Peste-des-Petits-Ruminants / Q000235:genetics / Q000276:immunology*; D018107:Peste-des-petits-ruminants virus / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D011110:Polymorphism, Genetic; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*; D014709:Vero Cells; D019562:Viral Load
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors