Long non-coding RNA BCAR4 is required for efficient influenza A virus replication

Abstract Long non-coding RNAs (lncRNAs) regulate diverse biological processes, including influenza A virus (IAV) infection. However, the understanding of lncRNAs in IAV infection is limited. By using both bioinformatic analyses and virological assays, we showed that lncRNA BCAR4 expression can be highly induced by infection of multiple different IAV subtypes. BCAR4 was required for the propagation of IAV infection. Genetic inactivation of BCAR4 inhibited IAV growth. Investigation of the IAV infection cycle revealed a suppressed IAV viral RNA transcription and replication, and attenuated viral protein synthesis in the BCAR4-deficient cells. BCAR4 potentially interacted with cellular splicing-associated proteins and the activation of BCAR4 was associated with influenza viral NS segment. These findings suggest the important role of lncRNA BCAR4 in regulation of IAV infection. Importance Long non-coding RNAs (lncRNAs) serve as critical regulators in the biological processes of influenza A virus (IAV) infection. However, how lncRNAs engage IAV infection remains unclear. Here we show BCAR4 as highly universally induced lncRNA in infection of multiple different IAV subtypes. Deletion of BCAR4 reduced IAV multiplication. In the IAV infection cycle, BCAR4 deficiency decreased IAV viral RNA transcription, replication and viral protein biosynthesis. BCAR4 was potentially binding to the host RNA splicing associated protein, and the IAV viral NS segment is required for the activation of BCAR4. Our results highlight important regulation of BCAR4 in IAV infection.