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bioRxiv · 10.1101/2022.01.05.475173

Hantaan virus replication is promoted via AKT activated mitochondria OXPHOS

Dong, Y.·Zhang, X.·Li, M.·Ying, Q.·Feng, Y.·Li, Z.·Wu, X.-a.·Wang, F.
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Abstract

Oxidative phosphorylation (OXPHOS) is a vital pathway provides ATP for intracellular activities. Here, we found that Hantaan virus (HTNV) exploited mitochondria OXPHOS to assist its replication in host cells and Protein Kinase B/AKT played a major function in this process. Inhibiting AKT activation by BEZ treatment can inhibit HTNV replication and prevent the increase of OXPHOS level caused by HTNV infection. We also found that HTNV infection can promote AKT translocation to mitochondria, where AKT phosphorylates Polynucleotide phosphorylase (PNPT). Taken together, our research demonstrates that HTNV replication exploits OXPHOS in host cells and it increases OXPHOS function by AKT-PNPT interaction in mitochondria. IMPORTANCEVirus depends on metabolic pathways in host cells to favor its replication. This is a vital process which needs complicated host-virus interaction and targeting this process is a new strategy for antiviral drug development. Hantaan virus (HTNV) is the major pathogen which causes Hemorrhagic Fever with Renal Syndrome (HFRS) in China. However, there are neither effective therapeutic drugs nor FDA-licensed vaccine against HFRS, a deeper understanding of HTNV infection characteristics is of great significance for global public health and safety. This research means to elucidate the major metabolic pathway exploited by HTNV during its replication in host cells and its underlying molecular mechanism, which can enrich our understanding about HTNV biological characteristics and pathogenesis, also provide a new view on anti-HTNV drug development.

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Dong, Y., Zhang, X., Li, M., Ying, Q., Feng, Y., Li, Z., Wu, X.-a., Wang, F.. 2022-01-06. Hantaan virus replication is promoted via AKT activated mitochondria OXPHOS. https://doi.org/10.1101/2022.01.05.475173

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