tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2024 Aug 1:2387910.
doi: 10.1080/22221751.2024.2387910. Online ahead of print. Inhibition of RAN Attenuates Influenza A Virus Replication and Nucleoprotein Nuclear Export
Lei Cao[SUP] 1 2 3 [/SUP], Ziwei She[SUP] 1 2 3 [/SUP], Ya Zhao[SUP] 1 2 3 [/SUP], Chuxing Cheng[SUP] 4 [/SUP], Yaqin Li[SUP] 4 [/SUP], Ting Xu[SUP] 1 2 3 [/SUP], Haiying Mao[SUP] 1 2 3 [/SUP], Yumei Zhang[SUP] 1 2 3 [/SUP], Xianfeng Hui[SUP] 1 2 3 [/SUP], Xian Lin[SUP] 1 2 3 [/SUP], Ting Wang[SUP] 1 2 3 [/SUP], Xiaomei Sun[SUP] 1 2 3 [/SUP], Kun Huang[SUP] 1 2 3 [/SUP], Lianzhong Zhao[SUP] 5 [/SUP], Meilin Jin[SUP] 1 2 3 6 [/SUP]
Affiliations
Nuclear export of the viral ribonucleoprotein (vRNP) is a critical step in the influenza A virus (IAV) life cycle and may be an effective target for the development of anti- IAV drugs. The host factor ras-related nuclear protein (RAN) is known to participates in the life cycle of several viruses, but its role in influenza virus replication remains unknown. In the present study, we aimed to determine the function of RAN in influenza virus replication using different cell lines and subtype strains. We found that RAN is essential for the nuclear export of vRNP, as it enhances the binding affinity of XPO1 toward the viral nuclear export protein NS2. Depletion of RAN constrained the vRNP complex in the nucleus and attenuated the replication of various subtypes of influenza virus. Using in silico compound screening, we identified bepotastine could dissociate the RAN-XPO1-vRNP trimeric complex and exhibit potent antiviral activity against influenza virus both in vitro and in vivo. This study demonstrates the important role of RAN in IAV replication and suggests its potential use as an antiviral agent.
Keywords: Influenza A virus, nuclear export, viral ribonucleoprotein, RAN, bepotastine.
. 2024 Aug 1:2387910.
doi: 10.1080/22221751.2024.2387910. Online ahead of print. Inhibition of RAN Attenuates Influenza A Virus Replication and Nucleoprotein Nuclear Export
Lei Cao[SUP] 1 2 3 [/SUP], Ziwei She[SUP] 1 2 3 [/SUP], Ya Zhao[SUP] 1 2 3 [/SUP], Chuxing Cheng[SUP] 4 [/SUP], Yaqin Li[SUP] 4 [/SUP], Ting Xu[SUP] 1 2 3 [/SUP], Haiying Mao[SUP] 1 2 3 [/SUP], Yumei Zhang[SUP] 1 2 3 [/SUP], Xianfeng Hui[SUP] 1 2 3 [/SUP], Xian Lin[SUP] 1 2 3 [/SUP], Ting Wang[SUP] 1 2 3 [/SUP], Xiaomei Sun[SUP] 1 2 3 [/SUP], Kun Huang[SUP] 1 2 3 [/SUP], Lianzhong Zhao[SUP] 5 [/SUP], Meilin Jin[SUP] 1 2 3 6 [/SUP]
Affiliations
- PMID: 39087696
- DOI: 10.1080/22221751.2024.2387910
Nuclear export of the viral ribonucleoprotein (vRNP) is a critical step in the influenza A virus (IAV) life cycle and may be an effective target for the development of anti- IAV drugs. The host factor ras-related nuclear protein (RAN) is known to participates in the life cycle of several viruses, but its role in influenza virus replication remains unknown. In the present study, we aimed to determine the function of RAN in influenza virus replication using different cell lines and subtype strains. We found that RAN is essential for the nuclear export of vRNP, as it enhances the binding affinity of XPO1 toward the viral nuclear export protein NS2. Depletion of RAN constrained the vRNP complex in the nucleus and attenuated the replication of various subtypes of influenza virus. Using in silico compound screening, we identified bepotastine could dissociate the RAN-XPO1-vRNP trimeric complex and exhibit potent antiviral activity against influenza virus both in vitro and in vivo. This study demonstrates the important role of RAN in IAV replication and suggests its potential use as an antiviral agent.
Keywords: Influenza A virus, nuclear export, viral ribonucleoprotein, RAN, bepotastine.