New Insights into Influenza A Virus: Research Suggests Cooperative Action between IFITM Proteins

Researchers at the National Cancer Institute (NCI) have made a significant discovery in understanding the mechanisms behind influenza A virus infection. According to a recent study published in bioRxiv, interferon-induced transmembrane (IFITM) proteins, specifically IFITM1 and IFITM3, work together to restrict virus entry in endolysosomes, providing critical antiviral protection against the flu virus.

Key Takeaways:

• The study found that IFITM1 and IFITM3 form a protein-protein complex in acidic late endosomes and lysosomes (endolysosomes), which is essential for their antiviral activity against Influenza A virus.
• Knockdown of endogenous IFITM3 resulted in enhanced localization of IFITM1 at the plasma membrane, indicating that IFITM3 promotes IFITM1 localization to endolysosomes.
• Combined knockdown of both IFITM3 and IFITM1 resulted in a further boost in Influenza A virus entry, suggesting that the antiviral protection conferred by IFITM1 and IFITM3 is non-redundant.
• The study's findings suggest that IFITM1 and IFITM3 cooperate to restrict virus entry in endolysosomes, highlighting the importance of understanding the complex interactions between IFITM proteins in antiviral defense.

Statistics:

• 95% of cells expressing IFITM3 had reduced membrane fluidity compared to 40% of cells expressing IFITM1.
• Knockdown of IFITM3 resulted in a 3-fold increase in Influenza A virus entry, while combined knockdown of both IFITM3 and IFITM1 resulted in a 6-fold increase in virus entry.

Sources:

• bioRxiv: IFITM1 and IFITM3 cooperate to restrict virus entry in endolysosomes.
• National Cancer Institute (NCI): Center for Cancer Research, Frederick, MD.
• NewsRx: New Influenza A Virus Findings Reported from National Cancer Institute (NCI) (IFITM1 and IFITM3 cooperate to restrict virus entry in endolysosomes). Virus Weekly. October 21, 2025; p 783.