| Summary: | 碩士 === 國立成功大學 === 分子醫學研究所 === 99 === The 8th genome segment of Influenza A Viruses (IAV) directs the synthesis of a collinear mRNA encoding for the non-structural protein 1 (NS1) and a spliced mRNA encoding for the nuclear export protein (NEP). While NS1 is largely known as a multi-regulatory factor in facilitating viral RNA replication and antagonizing host Inteferon response, little has been reported regarding the insight contribution of NEP and its cellular partners upon IAV replication. To gain a systemic view of cellular proteins participated in NEP-mediated activities, a Tandem Affinity Tag Purification based proteomic approach was employed and has identified 18 candidates with functional relevance in RNP trafficking, Pol-II transcriptional control, Janus kinase (JAK) signaling, or mitochondria ATP regulation. The first two categories match the predicted role of NEP in vRNA replication and nucleo-cytoplasmic transport of viral RNPs, while the last two categories may accord with novel activities of NEP in cell fates or cytokine regulation for viral multiplication. We report here that NEP interacts with mitochondria ATPsynthase F1 α/β subunits by co-immunoprecipitation assay and a confocal imaging analysis. In addition, NEP downregulated cellular ATP level, but did not affect mitochondria membrane potential or cause cellular ROS and apoptosis. As IAV, unlike many RNA viruses, lack of self-equipped motors similar to the α subunit of F1 to package their genomes, whether NEP hijacks ATP5synthase for vRNP packaging is under investigation. In addition, NEP antagonized type-1 IFN response, whether this links to the down regulated ATP level or the interference of JAK signaling pathway require further investigation. Collectively, our results reveal NEP as a multi-regulatory factor to influence ATP homeostasis and facilitate IAV egression and induced pathogenesis.
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