Peste des petits ruminants virus hemagglutinin (H) induces lysosomal degradation of host cyclophilin A to facilitate viral replication

Abstract

Peste des petits ruminants virus (PPRV) is a highly contagious disease that affects sheep and goats. To better understand PPRV replication and virulence, cyclophilin A (CypA), a multifunctional goat host protein, was selected for further studies. CypA has been reported to inhibit or facilitate viral replication. However, the precise roles of CypA during PPRV infection remain unclear. Our data show for the first time that CypA suppressed PPRV replication by its PPIase activity, and PPRV infection decreased CypA protein levels. Detailed analysis revealed that PPRV H protein was responsible for the reduction of CypA, which was dependent on the lysosome pathway. No interaction was identified between H and CypA. Furthermore, the 35–58 region of H was essential for the reduction of CypA. In conclusion, our findings identify the antiviral role of CypA against PPRV and provide key insights into how PPRV H protein antagonizes host antiviral response.