title: Synthetic Toll-like receptor 7 ligand inhibits porcine reproductive and respiratory syndrome virus infection in primary porcine alveolar macrophages.
abstract: Porcine reproductive and respiratory syndrome virus (PRRSV), a common viral pathogen, causes huge annual economic losses to the swine industry worldwide. After triggering by specific ligands, the Toll-like receptor 7 (TLR7), a type of pattern-recognition receptor (PRR), induces antiviral cytokines production. Previously, we synthesized an adenine analog, designated SZU101, a TLR7-specific ligand. In this study, we assessed the inhibitory effect of SZU101 on PRRSV infection in vitro. SZU101 significantly suppressed PRRSV infection in primary porcine alveolar macrophages (PAMs) in a dose-dependent manner. Moreover, SZU101-induced inhibition involved NF-κB pathway activation in PAMs to initiate expression of TLR7-mediated cytokines and induce expression of downstream signaling IFN-stimulated genes (ISGs). Chloroquine, a TLR7 inhibitor, and BAY 11-7082, an NF-κB inhibitor, reversed both the SZU101-induced antiviral effect and induction of cytokine genes and ISGs expression. Therefore, SZU101 antiviral effects depend at least in part on TLR7-NF-κB signaling pathway. Additionally, administration of SZU101 enhanced the humoral and cell-mediated immune responses against PRRSV antigens in mice. Given these results, SZU101 holds promise as an antiviral agent and a vaccine adjuvant to prevent PRRSV infection in pigs.
authors.affiliation: Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, Yangling, Shaanxi 712100, China. Electronic address: mututushen@163.com.
authors.forename: Yongkun
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, Yangling, Shaanxi 712100, China. Electronic address: taofengdu@nwsuaf.edu.cn.
authors.forename: Taofeng
authors.initials: T
authors.lastname: Du
authors.affiliation: Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, Yangling, Shaanxi 712100, China. Electronic address: ling.dongyi@163.com.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, Yangling, Shaanxi 712100, China. Electronic address: zhangangke1112@126.com.
authors.forename: Angke
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, Yangling, Shaanxi 712100, China. Electronic address: leofighting@163.com.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Cancer Research Center, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, China; Shenzhen Engineering Laboratory of Synthetic Biology, Shenzhen, Guangdong 518060, China. Electronic address: diaoyuwen@szu.edu.cn.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Diao
authors.affiliation: Cancer Research Center, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, China; Shenzhen Engineering Laboratory of Synthetic Biology, Shenzhen, Guangdong 518060, China. Electronic address: gyjin@szu.edu.cn.
authors.forename: Guangyi
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, Yangling, Shaanxi 712100, China. Electronic address: zhouem@nwsuaf.edu.cn.
authors.forename: En-Min
authors.initials: EM
authors.lastname: Zhou
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology; D000563:Amebicides / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D019316:Porcine respiratory and reproductive syndrome virus / Q000187:drug effects* / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013386:Succinates / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology; D013552:Swine; D051199:Toll-Like Receptor 7 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000563:Amebicides; D000998:Antiviral Agents; D016207:Cytokines; D016328:NF-kappa B; D009570:Nitriles; C000604281:SZU-101; D013386:Succinates; D013450:Sulfones; D051199:Toll-Like Receptor 7; D002738:Chloroquine; D000225:Adenine
keywords: Antivirus factor; ISGs; NF-κB; PRRSV; TLR7