BIK polymorphism and proteasome regulation unveil host risk factor for severe influenza.

ABSTRACT: Influenza A viruses (IAVs) pose a significant public health threat, with host factors playing a crucial role in disease severity. We investigated the role of Bcl-2-interacting killer (BIK) in IAV infection using cellular and mouse models, and influenza-infected human cohort. In airway epithelial cells (AECs), BIK deficiency impaired viral replication, while BIK restoration enhanced it. Conversely, airway-specific BIK overexpression in mice increased viral load, inflammation, and mortality, whereas BIK suppression conferred protection. Critically, a genetic variation (rs738276) in the BIK gene, influencing BIK expression, correlates with altered viral replication in air-liquid interface differentiated primary normal human bronchial epithelial cells and influenza severity in humans. M

SUBMITTER: Soni S 

PROVIDER: S-EPMC12280918 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature