Influenza A Virus Infection Induces Viral and Cellular Defective Ribosomal Products Encoded by Alternative Reading...

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• The role of alternative reading frame (ARF)-derived peptides in antiviral CD8⁺ T cell responses remains unclear.
• Influenza A virus (IAV) NS1 protein is crucial for viral evasion of host immunity.

Purpose of the Study:

• To investigate the immunogenicity of ARF-derived peptides during IAV infection.
• To characterize the CD8⁺ T cell response to a novel IAV-derived epitope.

Main Methods:

• Identification and synthesis of a predicted ARF-derived peptide epitope (NS1-ARF2_1-8).
• Assessment of T cell responses in IAV-infected BALB/c mice using ELISPOT assays.
• Analysis of peptide presentation from unspliced viral mRNA.

Main Results:

• The NS1-ARF2_1-8 epitope elicits a strong, functional CD8⁺ T cell response in IAV-infected mice.
• This epitope is presented from unspliced NS mRNA, originating from downstream translation initiation.
• The source peptide has no discernible biological function or impact on viral pathogenicity.

Conclusions:

• Antiviral immunity can leverage naturally occurring translational errors to generate functional CD8⁺ T cell responses.
• IAV infection can enhance cellular ARF translation, suggesting potential implications for virus-induced autoimmunity.