A novel TLR7 agonist exhibits antiviral activity against pseudorabies virus1

Abstract

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.