Influenza A virus-induced caspase-3 cleaves the histone deacetylase 6 in infected epithelial cells

Abstract 

Histone deacetylase 6 (HDAC6) is a multi-substrate cytoplasmic enzyme that regulates many important biological processes. Recently, some reports have implicated HDAC6 in viral infection. However, nothing is known about its regulation in virus-infected cells. The data presented here for the first time demonstrate the caspase-3-mediated cleavage of HDAC6 in influenza A virus (IAV)-infected cells. HDAC6 polypeptide contains the caspase-3 cleavage motif DMAD-S at the C-terminus, and is a caspase-3 substrate. The cleavage removes most of the C-terminal ubiquitin-binding zinc finger domain from HDAC6, which could be significant for HDAC6’s role in IAV-induced apoptosis in infected cells.

Abbreviations: BUZ, bound to ubiquitin zinc finger, HDAC, histone deacetylase, hsp90, heat-shock protein 90, IAV, influenza A virus, INF, infected, M1, matrix protein, MDCK, Madin-Darby canine kidney, NHBE, normal human bronchial epithelial, NP, nucleoprotein, SE14, serine-glutamic acid repeats, UNI, uninfected, vRNP, viral ribonucleoprotein

Keywords: Influenza A, Histone deacetylase 6, Caspase-3, Cleavage