An interferon-stimulated long non-coding RNA USP30-AS1 as an immune modulator in influenza A virus infection

• Published in: PLoS pathogens Vol. 21; no. 1; p. e1012854
• Main Authors: Cao, Yi, Chin, Alex W. H., Gu, Haogao, Li, Mengting, Gu, Yuner, Lau, Sylvia P. N., Hui, Kenrie P. Y., Chan, Michael C. W., Poon, Leo L. M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.01.2025; Public Library of Science (PLoS)
• Subjects: Animals; Biological response modifiers; Biology and life sciences; Control systems; Gene expression; Genes; Genetic aspects; Health aspects; Humans; Immune response; Immune system; Immunity, Innate; Immunotherapy; Influenza; Influenza A virus - immunology; Influenza, Human - genetics; Influenza, Human - immunology; Influenza, Human - virology; Interferon; Interferons - immunology; Medical research; Medicine and health sciences; Medicine, Experimental; Mice; Mice, Inbred C57BL; Orthomyxoviridae Infections - genetics; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - virology; Physiological aspects; Protein biosynthesis; Research and Analysis Methods; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - immunology; Signal Transduction; Viral proteins; China; Puerto Rico; California
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1012854

Long non-coding RNAs (lncRNAs) are essential components of innate immunity, maintaining the functionality of immune systems that control virus infection. However, how lncRNAs engage immune responses during influenza A virus (IAV) infection remains unclear. Here, we show that lncRNA USP30-AS1 is up-regulated by infection of multiple different IAV subtypes and is required for tuning inflammatory and antiviral response in IAV infection. Genetically inactivation of USP30-AS1 enhances viral protein synthesis and viral growth. USP30-AS1 is an interferon-stimulated gene, and the induction of USP30-AS1 can be achieved by JAK-STAT mediated signaling activation. The immune regulation of USP30-AS1 is independent of its proximal protein-coding gene USP30 . In IAV infection, deletion of USP30-AS1 unleashes high systemic inflammatory responses involving a broad range of pro-inflammatory factors, suggesting USP30-AS1 as a critical modulator of immune responses in IAV infection. Furthermore, we established a database providing well-annotated host gene expression profiles IAV infection or immune stimulation.