SNHG15 Positively Regulates Influenza Virus Infection Through Its Association With miR-153 and RABL2A

Area of Science:

• Molecular Biology
• Virology
• Genetics

Background:

• Influenza viruses cause seasonal epidemics with current vaccines offering incomplete protection.
• Long non-coding RNAs (lncRNAs) are key regulators of biological processes, including viral infections.
• Understanding host factors that influence influenza virus infection is crucial for developing new antiviral strategies.

Purpose of the Study:

• To investigate the role of lncRNAs in influenza virus infection.
• To identify specific lncRNAs that modulate influenza virus replication.
• To elucidate the molecular mechanisms by which identified lncRNAs affect viral pathogenesis.

Main Methods:

• Identification of differentially expressed lncRNAs upon influenza virus infection.
• CRISPR interference (CRISPRi) and RNA interference (RNAi) for gene knockdown.
• Quantitative real-time PCR, RNA pull-down assays, and mass spectrometry.
• Overexpression studies and assessment of viral replication and internalization.

Main Results:

• Seventeen lncRNAs were found to be altered by influenza virus infection.
• The lncRNA SNHG15 was identified as a proviral factor, enhancing influenza virus infection.
• Knockdown of SNHG15 reduced viral infection, while its overexpression increased viral replication.
• miR-153-3p acted as an anti-influenza microRNA, counteracting SNHG15's effects.
• SNHG15 interacts with RABL2A, and both facilitate influenza virus internalization.

Conclusions:

• SNHG15 significantly enhances influenza A virus infection.
• The proviral activity of SNHG15 is mediated through its interactions with miR-153 and RABL2A.
• SNHG15 and RABL2A cooperate to promote viral entry into host cells.