Influenza virus neuraminidase regulates host CD8⁺ T-cell response in mice

Influenza A virus (IAV)-specific CD8⁺ T-cell response was shown to provide protection against pandemic and seasonal influenza infections. However, the response was often relatively weak and the mechanism was unclear. Here, we show that the composition of IAV released from infected cells is regulated by the neuraminidase (NA) activity and the cells infected by NA-defective virus cause intracellular viral protein accumulation and cell death. In addition, after uptake of NA-defective viruses by dendritic cells (DCs), an expression of the major histocompatibility complex class I is induced to activate IAV-specific CD8⁺ T-cell response. When mice were infected by NA-defective IAV, a CD8⁺ T-cell response to the highly conserved viral antigens including PB1, NP, HA, M1, M2 and NS1 was observed along with the increasing expression of IL10, IL12 and IL27. Vaccination of mice with NA-defective H1N1 A/WSN/33 induced a strong IAV-specific CD8⁺ T cell response against H1N1, H3N2 and H5N1. This study reveals the role of NA in the IAV-specific CD8⁺ T-cell response and virion assembly process, and provides an alternative direction toward the development of universal influenza vaccines.