Breaking the PRRSV-2 Life Cycle in Porcine Alveolar Macrophages: Tylvalosin’s Multi-Stage Inhibition

Porcine reproductive and respiratory syndrome (PRRS) is one of the most serious diseases threatening the swine industry worldwide. However, no satisfactory control strategy has existed until now. In this study, the effectiveness of tylvalosin against PRRSV and the underlying mechanism was investigated. The results showed that in porcine alveolar macrophages (PAMs), tylvalosin can inhibit the replication of the NADC30-like and NADC34-like strains in a dose-dependent manner. It is worth noting that pre-incubation with tylvalosin had no significant inhibitory effect on the NADC30-like strain but did inhibit the NADC34-like strain. Co-incubation of both viruses and tylvalosin or post-incubation with tylvalosin after viral infection inhibited PRRSV. We further analyzed the effect of tylvalosin on different stages of PRRSV replication and found that the stages in the PRRSV life cycle could be blocked by tylvalosin. Tylvalosin has an antiviral effect on all four stages of the NADC34-like strain's infectious cycle but has no effect against the adsorption phase of the NADC30-like strain. These results demonstrated that tylvalosin suppressed PRRSV infection in PAMs and inhibited PRRSV infection at multiple steps of the viral life cycle. This study will contribute to the clinical prevention and control of PRRS and provide a basis for further exploration of the anti-PRRSV effects of tylvalosin.