CircMYO9A inhibits influenza A virus replication by dampening haemagglutinin cleavage via increasing SERPINE1/PAI-1 expression

Circular RNAs (circRNAs) represent a class of widespread and diverse covalently closed circular endogenous RNAs that play critical roles in regulating gene expression in mammals. However, the roles and regulatory mechanisms of circRNAs during influenza A virus (IAV) infection remain largely unexplor...

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Main Authors: Yiqing Zheng, Xiaoting Zhang, Zhiyuan Liu, Menglu Fan, Lulu Deng, Jihui Ping
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2025.2502007
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author Yiqing Zheng
Xiaoting Zhang
Zhiyuan Liu
Menglu Fan
Lulu Deng
Jihui Ping
author_facet Yiqing Zheng
Xiaoting Zhang
Zhiyuan Liu
Menglu Fan
Lulu Deng
Jihui Ping
author_sort Yiqing Zheng
collection DOAJ
description Circular RNAs (circRNAs) represent a class of widespread and diverse covalently closed circular endogenous RNAs that play critical roles in regulating gene expression in mammals. However, the roles and regulatory mechanisms of circRNAs during influenza A virus (IAV) infection remain largely unexplored. In this study, we screened the circRNA transcription profiles of WSN-infected cells to identify circRNAs involved in viral replication and identified a novel differentially expressed circular RNA, circMYO9A. Mechanistically, circMYO9A acts as a competing endogenous RNA (ceRNA) for SERPINE1/PAI-1 by sponging miR-6059-3p, thereby increasing SERPINE1/PAI-1 expression, which restricts IAV haemagglutinin cleavage and subsequently reduces the infectivity of progeny viruses. Importantly, our findings demonstrate that circMYO9A significantly inhibits viral replication in the lungs of infected mice, potentially increasing their survival during IAV infection. These results demonstrate that circRNAs play crucial roles in inhibiting IAV replication and provide novel insights into potential therapeutic strategies involving circRNAs.
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institution OA Journals
issn 2222-1751
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publishDate 2025-12-01
publisher Taylor & Francis Group
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series Emerging Microbes and Infections
spelling doaj-art-f367955a5e034cffae82de25614cab4c2025-08-20T01:55:21ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2025.2502007CircMYO9A inhibits influenza A virus replication by dampening haemagglutinin cleavage via increasing SERPINE1/PAI-1 expressionYiqing Zheng0Xiaoting Zhang1Zhiyuan Liu2Menglu Fan3Lulu Deng4Jihui Ping5MOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, People’s Republic of ChinaMOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, People’s Republic of ChinaMOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, People’s Republic of ChinaMOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, People’s Republic of ChinaMOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, People’s Republic of ChinaMOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, People’s Republic of ChinaCircular RNAs (circRNAs) represent a class of widespread and diverse covalently closed circular endogenous RNAs that play critical roles in regulating gene expression in mammals. However, the roles and regulatory mechanisms of circRNAs during influenza A virus (IAV) infection remain largely unexplored. In this study, we screened the circRNA transcription profiles of WSN-infected cells to identify circRNAs involved in viral replication and identified a novel differentially expressed circular RNA, circMYO9A. Mechanistically, circMYO9A acts as a competing endogenous RNA (ceRNA) for SERPINE1/PAI-1 by sponging miR-6059-3p, thereby increasing SERPINE1/PAI-1 expression, which restricts IAV haemagglutinin cleavage and subsequently reduces the infectivity of progeny viruses. Importantly, our findings demonstrate that circMYO9A significantly inhibits viral replication in the lungs of infected mice, potentially increasing their survival during IAV infection. These results demonstrate that circRNAs play crucial roles in inhibiting IAV replication and provide novel insights into potential therapeutic strategies involving circRNAs.https://www.tandfonline.com/doi/10.1080/22221751.2025.2502007Influenza viruscircMYO9ASERPINE1CeRNAhaemagglutinin cleavage
spellingShingle Yiqing Zheng
Xiaoting Zhang
Zhiyuan Liu
Menglu Fan
Lulu Deng
Jihui Ping
CircMYO9A inhibits influenza A virus replication by dampening haemagglutinin cleavage via increasing SERPINE1/PAI-1 expression
Emerging Microbes and Infections
Influenza virus
circMYO9A
SERPINE1
CeRNA
haemagglutinin cleavage
title CircMYO9A inhibits influenza A virus replication by dampening haemagglutinin cleavage via increasing SERPINE1/PAI-1 expression
title_full CircMYO9A inhibits influenza A virus replication by dampening haemagglutinin cleavage via increasing SERPINE1/PAI-1 expression
title_fullStr CircMYO9A inhibits influenza A virus replication by dampening haemagglutinin cleavage via increasing SERPINE1/PAI-1 expression
title_full_unstemmed CircMYO9A inhibits influenza A virus replication by dampening haemagglutinin cleavage via increasing SERPINE1/PAI-1 expression
title_short CircMYO9A inhibits influenza A virus replication by dampening haemagglutinin cleavage via increasing SERPINE1/PAI-1 expression
title_sort circmyo9a inhibits influenza a virus replication by dampening haemagglutinin cleavage via increasing serpine1 pai 1 expression
topic Influenza virus
circMYO9A
SERPINE1
CeRNA
haemagglutinin cleavage
url https://www.tandfonline.com/doi/10.1080/22221751.2025.2502007
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