Cell Stress: Survival and Apoptosis

The multifunctional polydnavirus ANK1 protein: new insights for apoptotis pathway. Mammalians and insects, although phylogenetically distant, share some conserved pathways. One of these is the apoptosis involved in physiological and pathological conditions. The induction of apoptosis is one of the most common strategies adopted by various polydnaviruses (PDVs) to suppress the immune response of insect hosts. PDVs are obligate symbionts of parasitoid wasps attacking exclusively larval stages of their lepidopteran hosts. PDVs DNA is integrated into the genome of the parasitoid and vertically transmitted through the germline. The PDVs particles selectively infect host tissues expressing their genes without undergoing any replication events. In this work we studied the model system host-parasitoid, Heliothis virescens/Toxoneuron nigriceps, focusing on the role of the viral gene T. nigriceps Bracovirus ank 1(TnBVank1) in the apoptosis. TnBVank1 encodes an ankyrin motif protein similar to the mammalian IkB, an inhibitor of the transcription nuclear factor kB. The role of TnBVank1 was investigated in H. virescens haemocytes, by in vivo transient expression and, in vitro, in Drosophila Schneider’s S2 cells which stably expressed TnBVank1. Apoptosis was detected by caspase-3 activity and Tunel staining. ANK1 interactor proteins were reveled by coimmunoprecipitation experiments which indicated that ANK1 bound Alix, an interactor of apoptosis-linked gene protein 2 (ALG-2). Alix was silenced by RNAi to study the function of ANK1-Alix interaction. Here we show that when ANK1 was stably expressed in S2 cells stimulated caspase-3 activity. Furthermore we get the same results into H. virescens haemocytes by in vivo transient expression of TnBVank1. Silencing Alix, ANK1 was no longer able to cause apoptosis in S2 cells and into H. virescens haemocytes. Collectively, these results indicate that ANK1 induces apoptosis by interacting with Alix, suggesting that this role could be relevant in the suppression of host immune response observed in larvae parasitized by T. nigriceps