Microplitis bicoloratus bracovirus regulates cyclophilin A-apoptosis-inducing factor interaction to induce cell apoptosis in the insect immunosuppressive process.

Abstract

Microplitis bicoloratus bracovirus (MbBV) induces apoptosis in hemocytes of the host (Spodoptera litura) via the cyclophilin A (CypA)‐mediated signaling pathway. However, the mechanisms underlying CypA‐mediated signaling during apoptosis remain largely unknown. Therefore, in this study, we investigated how CypA and apoptosis‐inducing factor (AIF) interact during MbBV‐mediated apoptosis. Our findings showed that MbBV induces apoptosis through the CypA‐AIF axis of insect immune suppression. In MbBV‐infected Spli221 cells, both the expression of the cypa gene and the release of AIF from the mitochondria increased the number of apoptotic cells. CypA and AIF underwent concurrent cytoplasm‐nuclear translocation. Conversely, blocking of AIF release from mitochondria not only inhibited the CypA‐AIF interaction but also inhibited the cytoplasmic‐nuclear translocation of AIF and CypA. Importantly, the survival of the apoptotic phenotype was significantly rescued in MbBV‐infected Spli221 cells. In addition, we found that the cyclosporine A‐mediated inhibition of CypA did not prevent the formation of the CypA and AIF complex; rather, this only suppressed genomic DNA fragmentation. In vitro experiments revealed direct molecular interactions between recombinant CypA and AIF. Taken together, our results demonstrate that the CypA‐AIF interaction plays an important role in MbBV‐induced innate immune suppression. This study will help to clarify aspects of insect immunological mechanisms and will be relevant to biological pest control.