Monocyte apoptotic bodies are vehicles for influenza A virus propagation

单核细胞凋亡小体是甲型流感病毒传播的载体

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作者:Georgia K Atkin-Smith, Mubing Duan, Damien J Zanker, Liyen Loh, Thi H O Nguyen, Marios Koutsakos, Tien Nguyen, Xiangrui Jiang, Julio Carrera, 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, 

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.

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