title: Molecular characterization of porcine SARM1 and its role in regulating TLRs signaling during highly pathogenic porcine reproductive and respiratory syndrome virus infection in vivo.
abstract: Toll-like receptors (TLRs) are important pattern-recognition receptors (PRRs) that trigger innate immune response and mediate acquired immunity. Evidence has shown that SARM1 (sterile-α and TIR motif containing protein 1) is one of five TIR domain-containing adaptor proteins involved in TLRs signaling transduction. In the present study, a full-length cDNA sequence was cloned for the porcine SARM1 gene, which contains nine exons. Using the radiation hybrid mapping approach, we assigned the porcine gene to SSC12 q13. Under the normal condition, porcine SARM1 was highly expressed in brain and spleen. Polyinosinic-polycytidylic acid (poly (I:C)) weakly induced the porcine SARM1 expression in the early stimulation. We found that porcine SARM1 protein is localized in mitochondria and attenuates NF-κB activation induced by stimulation and infection. The quantitative real-time PCR (Q-PCR) analysis showed that the expression of porcine SARM1 significantly decreased in several tissues of Tongcheng pigs infected with highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV). Gene-interaction network analysis for porcine SARM1 in porcine alveolar macrophages (PAMs) showed that down-regulation of SARM1 gene in infected Tongcheng pig may modulate TRIF-depend TLRs signaling and regulate the expression of disease-resistant genes and inflammatory genes. Our findings provide evidence that porcine SARM1 may play an important role in immune regulation with PRRSV infection.
authors.affiliation: Key Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education & Key Lab of Swine Genetics and Breeding of Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070 Hubei, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.forename: Tengfei
authors.initials: T
authors.lastname: Jiang
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Du
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Jiang
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Michal
authors.forename: Bang
authors.initials: B
authors.lastname: Liu
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000276:immunology*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000821:virology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013552:Swine / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
chemical_list: D051186:Armadillo Domain Proteins; D003598:Cytoskeletal Proteins; D016328:NF-kappa B; D051193:Toll-Like Receptors