RT Journal Article
SR Electronic
T1 Hantaan virus replication is promoted via AKT activated mitochondria OXPHOS
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.05.475173
DO 10.1101/2022.01.05.475173
A1 Dong, Yuhang
A1 Zhang, Xiaoxiao
A1 Li, Mengyang
A1 Ying, Qikang
A1 Feng, Yunan
A1 Li, Zhoupeng
A1 Wu, Xingan
A1 Wang, Fang
YR 2022
UL http://biorxiv.org/content/early/2022/01/06/2022.01.05.475173.abstract
AB 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.IMPORTANCE Virus 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.