Innate immunity is the primary defense against viral infections,with Toll-like receptors(TLRs) playing a crucial role in this process.This study aims to highlight the effectiveness of a pyrrolo[3,2-d]pyrimidine deriva...Innate immunity is the primary defense against viral infections,with Toll-like receptors(TLRs) playing a crucial role in this process.This study aims to highlight the effectiveness of a pyrrolo[3,2-d]pyrimidine derivative(named TLR713),a potential TLR7 agonist,in inhibiting pseudorabies virus(PRV) replication both in vitro and in vivo.Tests on PK-15 cells demonstrated that TLR713 had no significant impact on cell viability,cell cycle progression,or apoptosis at concentrations of 0–3 μmol L^(–1).TLR713 could promote the phosphorylation of IκBα,p38,and JNK through TLR7,and increase the expression of inflammatory cytokines.In vitro,when cells were treated with TLR713,PRV proliferation was inhibited via TLR7 pathway.Analysis of the viral life cycle indicated that TLR713 could inhibit the replication of PRV,but not affect viral attachment,entry,assembly,or release.In vivo,TLR713 showed no side effects on mice at a concentration of 25 mg kg^(–1).It improved the survival rate of PRV-infected mice,reduced tissue viral load,and alleviated the inflammatory response.In summary,this study highlights the potential of TLR713 as a novel TLR7 agonist capable of inhibiting PRV replication and may offer new opportunities for developing antiviral therapies.展开更多
基金financially supported by the Key R&D Special Project of Henan Province,China (241111110300)the National Natural Science Foundation of China (32402849)+2 种基金the Department of Henan Science and Technology,China (252102110035)the Doctoral Research Initiation Fund of Henan University of Animal Husbandry and Economy,China (2022HNUAHEDF033)Key Research Projects of Higher Education Institutions in Henan Province,China (25A150025)。
文摘Innate immunity is the primary defense against viral infections,with Toll-like receptors(TLRs) playing a crucial role in this process.This study aims to highlight the effectiveness of a pyrrolo[3,2-d]pyrimidine derivative(named TLR713),a potential TLR7 agonist,in inhibiting pseudorabies virus(PRV) replication both in vitro and in vivo.Tests on PK-15 cells demonstrated that TLR713 had no significant impact on cell viability,cell cycle progression,or apoptosis at concentrations of 0–3 μmol L^(–1).TLR713 could promote the phosphorylation of IκBα,p38,and JNK through TLR7,and increase the expression of inflammatory cytokines.In vitro,when cells were treated with TLR713,PRV proliferation was inhibited via TLR7 pathway.Analysis of the viral life cycle indicated that TLR713 could inhibit the replication of PRV,but not affect viral attachment,entry,assembly,or release.In vivo,TLR713 showed no side effects on mice at a concentration of 25 mg kg^(–1).It improved the survival rate of PRV-infected mice,reduced tissue viral load,and alleviated the inflammatory response.In summary,this study highlights the potential of TLR713 as a novel TLR7 agonist capable of inhibiting PRV replication and may offer new opportunities for developing antiviral therapies.
