Enhanced Natural Killer Cell Activity Could Counter Influenza Virus Immune Response Evasion

Influenza viruses use their neuraminidase (NA) proteins to escape natural killer (NK) cell killing by impairing the NK cells' NKp46 surface receptor recognition of the viruses.

Investigators at the Hebrew University of Jerusalem (Israel) considered an additional function for neuraminidase in influenza virus infectivity that was linked to the role of NK cells in controlling influenza infection.

The investigators described in the April 18, 2013, issue of the journal Cell Reports an immune-evasion mechanism of influenza viruses that was mediated by the NA protein. By using various NA blockers, they showed that NA removed sialic acid residues from NKp46, and that this led to reduced recognition of HA. Furthermore, they provided in vivo and in vitro evidence for the existence of this NA-mediated, NKp46-dependent immune-evasion mechanism and demonstrated that NA inhibitors, which are commonly used for the treatment of influenza infections, were useful not only as blockers of virus budding but also as boosters of NKp46 recognition.

Influenza viruses mutate and change NA structure so that drugs directed at NA can no longer bind this protein. Nonetheless, this type of widely used drug has the effect of boosting NK cell activity, enabling them to better eliminate the influenza virus. The investigators stress, therefore, that efforts should be focused on developing effective new drugs that would maintain and enhance NK cell activity, without inducing changes in viral NA protein structure.