Immunomodulatory Transcription Factor BATF2 regulates the Interferon Stimulated Genes Expression during Influenza A virus Infection

The basic leucine zipper ATF-like transcription factor 2 (BATF2) is involved in regulating immune, inflammatory, and antitumor responses. However, its role in viral infections, particularly influenza virus, remains poorly understood. This study delves into the influence of BATF2 expression on influenza virus replication and the innate immune response in pulmonary epithelial cells. Using interfered BATF2 expression in cells, we observed restriction in influenza A virus replication, accompanied by an increase in the expression of interferon-stimulated genes (ISGs), whereas the transcription factor Blimp-1 expression was decreased. Conversely, overexpression of BATF2 in A549 cells supported influenza virus replication and suppressed the expression of ISGs and pro-inflammatory cytokines. Notably, BATF2 overexpression was correlated with elevated expression of Blimp-1. These findings collectively suggest that BATF2 plays a role in modulating the innate immune response during influenza virus infection, influencing viral replication. The balanced expression of BATF2 helps regulate cytokine expression and cellular responses, thereby preventing excessive inflammation and cytokine storms. Our study provides insights into the intricate interplay between BATF2, innate immune responses, and viral infection. Understanding the precise mechanisms through which BATF2 regulates immune responses and along with Blimp-1 helps to initiate the cellular immune response during viral infections may have implications for the development of therapeutic strategies. Further investigations are warranted to elucidate the detailed functions of BATF2 in viral infections and explore its potential as a therapeutic target.