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Front Immunol . CircZFYVE1 functions as a competitive endogenous RNA to enhance LSM14A-mediated antiviral defense against influenza A virus

tetano

Editor, Senior Moderator
Front Immunol


. 2026 Jul 9:17:1841925.
doi: 10.3389/fimmu.2026.1841925. eCollection 2026.
CircZFYVE1 functions as a competitive endogenous RNA to enhance LSM14A-mediated antiviral defense against influenza A virus

Bingchen Qiao[SUP] #[/SUP][SUP] 1 [/SUP], Yiqing Zheng[SUP] #[/SUP][SUP] 1 [/SUP], Xiaoting Zhang[SUP] 1 [/SUP], Menglu Fan[SUP] 1 [/SUP], Zhiyuan Liu[SUP] 1 [/SUP], Linjuan Wu[SUP] 1 [/SUP], Juan Su[SUP] 1 [/SUP], Jihui Ping[SUP] 1 [/SUP]


Affiliations
Abstract

Introduction: Circular RNAs (circRNAs) are covalently closed endogenous RNAs that regulate gene expression at the post transcriptional level and have been implicated in antiviral immunity. However, their functional roles and regulatory mechanisms during influenza A virus (IAV) infection remain incompletely defined.
Methods: circZFYVE1 expression was profiled in A549 cells infected with the WSN strain of IAV using RT qPCR under time course and dose response conditions. The mechanistic function of circZFYVE1 was investigated through miRNA target prediction, luciferase reporter assays, and functional assays assessing its role as a competing endogenous RNA (ceRNA) and its impact on innate antiviral signaling.
Results: circZFYVE1 expression was induced in a time and dose dependent manner following WSN infection. Mechanistically, circZFYVE1 acts as a ceRNA by sponging hsa miR 4435, thereby relieving miRNA mediated suppression of the processing body associated protein LSM14A and enhancing innate antiviral signaling during infection.
Discussion: These findings define a circRNA-miRNA-mRNA regulatory axis that links IAV infection to innate antiviral responses, providing new insights into circRNA mediated host defenses. The circZFYVE1/LSM14A pathway represents a potential target for future studies aimed at modulating endogenous antiviral immunity.

Keywords: LSM14A; ceRNA; circRNA; circZFYVE1; influenza A virus.

 
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