A Human Long Non-coding RNA LncATV Promotes Virus Replication Through Restricting RIG-I-Mediated Innate Immunity

Area of Science:

• Immunology
• Molecular Biology
• Virology

Background:

• Pattern recognition receptors initiate innate immune responses against pathogens.
• Long non-coding RNAs (lncRNAs) are increasingly recognized as key biological regulators.
• The role of lncRNAs in the human antiviral innate immune response remains largely unexplored.

Purpose of the Study:

• To characterize the function of a novel human-specific lncRNA, lncATV, in the antiviral innate immune response.
• To investigate the mechanism by which lncATV regulates antiviral immunity.

Main Methods:

• Quantitative analysis of lncATV expression upon IFN stimulation and viral infection.
• Assessment of lncATV subcellular localization.
• Functional studies involving lncATV knockdown and overexpression in various cell types.
• Viral replication assays for multiple RNA viruses.
• RNA immunoprecipitation to identify interacting proteins.

Main Results:

• lncATV expression is upregulated by type I/III IFNs and viral infections.
• lncATV knockdown significantly inhibits replication of Hepatitis C virus, Zika virus, Newcastle disease virus, and Sendai virus.
• lncATV knockdown enhances RIG-I antiviral signaling and IFN pathways, while overexpression inhibits them.
• lncATV was found to associate with RIG-I.

Conclusions:

• lncATV acts as a negative regulator of the human antiviral innate immune response.
• This study identifies a novel mechanism of viral restriction mediated by a human-specific lncRNA.
• lncATV represents a potential therapeutic target for viral infections.