Objective Based on the preliminary transcriptome profiles of A549 cells responding to influenza A virus (IAV) infection, one of the most significantly up-regulated host circular RNA(circRNA), hsa_circ_004389, was selected to further validate its expression and explore its roles in IAV replication.

Method First, real-time quantitative PCR (qPCR) was used to verify the expression levels of hsa_circ_ 004389 at different time courses and different multiplicity of infection (MOI) of IAV infection in A549 cells; Second, hsa_circ_ 004389 expression in A549 cells treated with poly: I∶C (polyinosinic acid ∶ polycytidylic acid) and LPS (Lipopolysaccharide) were detected, respectively; Third, A549 cells were treated with interferon beta (IFNβ) and JAK inhibitor, and the expression of hsa_circ_004389 was determined; Finally, after a transient overexpression and knockdown in A549 cells, IAV replication at mRNA and protein levels were determined.

Result There was a positive correlation between the expression of hsa_circ_004389 and IAV replication. JAK-STAT signaling path was involved in regulating hsa_circ_004389 expression, and hsa_circ_004389 had the ability to inhibit IAV replication.

Conclusion Hsa_circ_004389, the product of the host responding to IAV infection, is a potential host anti-IAV factor.