Long non-coding RNAs (lncRNAs) are regulatory RNAs that interact with DNA, RNA, and proteins to influence physiological and disease processes. During viral infection, several host lncRNAs show altered expression and can modulate virus–host interactions. The study summarized here identifies a novel chicken antisense lncRNA, ckATP1A1-AS1, and describes its antiviral activity against influenza A virus (IAV) through a combination of innate immune regulation and direct interference with viral replication machinery.
The authors report that ckATP1A1-AS1 expression is induced upon IAV infection. The lncRNA was identified as IAV-responsive and characterized as a host factor with antiviral properties in the experimental systems used. The source notes that ckATP1A1-AS1 is transcriptionally upregulated during infection, a process further linked mechanistically to the transcription factor JUN.
Functional analyses in the study demonstrated that manipulating ckATP1A1-AS1 levels alters IAV replication. Specifically, overexpression of ckATP1A1-AS1 restricted infection by multiple IAV subtypes, whereas knockdown of ckATP1A1-AS1 enhanced viral replication. These observations establish a causal relationship between ckATP1A1-AS1 abundance and viral replication efficiency in the models described.
Mechanistic investigation identified the transcription factor JUN as an upstream activator of ckATP1A1-AS1. During IAV infection, JUN transcriptionally activates the lncRNA, linking infection-triggered signaling to increased ckATP1A1-AS1 expression. The source reports this regulatory step as part of the pathway by which IAV infection leads to elevated ckATP1A1-AS1 levels.
Downstream of its induction, ckATP1A1-AS1 promotes innate immune signaling. The lncRNA enhances expression of interferon-β and several key interferon-stimulated genes (ISGs), thereby positively regulating the type I interferon response. This immunomodulatory effect forms one arm of the antiviral activity attributed to ckATP1A1-AS1 in the study.
In addition to modulating host immunity, ckATP1A1-AS1 was shown to interact directly with the viral nucleoprotein (NP). The source reports a direct binding interaction between the lncRNA and NP, which enables ckATP1A1-AS1 to interfere with NP functions required for viral replication.
The interaction between ckATP1A1-AS1 and NP has multiple mechanistic consequences. The lncRNA competitively disrupts NP binding to importin α5, a cellular factor required for nuclear import of NP-containing complexes. In parallel, ckATP1A1-AS1 impairs NP oligomerization. Combined, these effects block the nuclear import of viral ribonucleoprotein complexes (vRNPs) and interfere with the assembly steps that require NP multimerization.
By preventing proper NP–importin α5 interaction and NP oligomer formation, ckATP1A1-AS1 suppresses vRNP assembly. The source states that this suppression leads to reduced viral polymerase activity, representing a second, direct antiviral mechanism in addition to the lncRNA’s enhancement of type I interferon signaling. Together, these mechanisms constrain multiple steps of the IAV replication cycle.
The study establishes ckATP1A1-AS1 as a dual-function antiviral lncRNA that both coordinates innate immune signaling and directly targets viral protein functions required for replication. Its transcriptional activation by JUN, ability to enhance interferon-β and ISG expression, and direct interference with NP–importin α5 binding and NP oligomerization define a multifaceted host defense role. These observations identify ckATP1A1-AS1 as a novel host factor that restricts IAV replication by acting at the level of immune modulation and by disrupting key viral replication steps.
Note: The source abstract provides the experimental conclusions and mechanistic model summarized here. Detailed experimental methods, quantitative data, cell types, animal models, or additional controls were not reported in the provided source excerpt and therefore are not described above.