Monocyte apoptotic bodies are vehicles for influenza A virus propagation
Georgia K. Atkin‐Smith, Mubing Duan, Damien Zanker, Liyen Loh, Thi H. O. Nguyen, Marios Koutsakos, Tien K. Nguyen, Xiangrui Jiang, Julio Carrera Montoya, Thanh Kha Phan, Chuanxin Liu, Stephanie Paone, Sara Oveissi, Amy L. Hodge, Amy A. Baxter, Katherine Kedzierska, Jason M. Mackenzie, Mark D. Hulett, Pamuk Bilsel, Weisan Chen, Ivan K. H. Poon
Abstract
The disassembly of apoptotic cells into small membrane-bound vesicles termed apoptotic bodies (ApoBDs) is a hallmark of apoptosis; however, the functional significance of this process is not well defined. We recently discovered a new membrane protrusion (termed beaded apoptopodia) generated by apoptotic monocytes which fragments to release an abundance of ApoBDs. To investigate the function of apoptotic monocyte disassembly, we used influenza A virus (IAV) infection as a proof-of-concept model, as IAV commonly infects monocytes in physiological settings. We show that ApoBDs generated from IAV-infected monocytes contained IAV mRNA, protein and virions and consequently, could facilitate viral propagation in vitro and in vivo, and induce a robust antiviral immune response. We also identified an antipsychotic, Haloperidol, as an unexpected inhibitor of monocyte cell disassembly which could impair ApoBD-mediated viral propagation under in vitro conditions. Together, this study reveals a previously unrecognised function of apoptotic monocyte disassembly in the pathogenesis of IAV infections.