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Virology . Transcriptome screening identifies circRNA-INSR as a novel host factor associated with avian influenza virus replication

tetano

Editor, Senior Moderator
Virology

. 2026 Sep 4:625:111072.
doi: 10.1016/j.virol.2026.111072. Online ahead of print.

Transcriptome screening identifies circRNA-INSR as a novel host factor associated with avian influenza virus replication​


Zhiyuan Liu 1 , Menglu Fan 1 , Yiqing Zheng 1 , Yiran Zeng 1 , Lulu Deng 1 , Yusen Tian 1 , Juan Su 2 , Jihui Ping 3

Affiliations


Abstract​


Circular RNAs (circRNAs) represent a class of covalently closed non-coding RNA molecules that exert vital regulatory effects on host-pathogen interplay. The H9N2 subtype of avian influenza virus (AIV) is a widespread pathogen on a global scale, inflicting considerable economic damage to the poultry sector and harboring potential risks of cross-species transmission to humans. Despite growing evidence suggesting that non-coding RNAs can modulate the replication of influenza viruses, the expression patterns and functions of avian-derived circRNAs during H9N2 AIV infection have been largely unclear. Here, we conducted a systematic investigation into the expression dynamics of circRNAs in DF1 cells infected with H9N2 AIV by high-throughput RNA sequencing technology. A total of 139 differentially expressed circRNAs were identified, with 58 exhibiting upregulation and 81 showing downregulation relative to non-infected control cells. Of note, a circRNA originating from exon 2 of the insulin receptor (INSR) gene displayed consistent upregulation during viral infection. Functional assays verified its contributing role in the replication of H9N2 AIV. Specifically, siRNA-mediated knockdown of circ-INSR significantly suppressed H9N2 AIV replication. This study is the first to identify circ-INSR as a host factor contributing to influenza virus replication. Our results provide a basis for developing circRNA-based strategies against H9N2 avian influenza virus.

Keywords: Avian influenza virus; Circ-INSR; Competing endogenous RNA; High-throughput sequencing; Viral replication.
 
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