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Published on: November 4, 2015
Monocyte apoptotic bodies are vehicles for influenza A virus propagation
Georgia K Atkin-Smith1, Mubing Duan2, Damien J Zanker1
1Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia.
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.
Insights
Apoptotic monocytes release viral particles via apoptotic bodies (ApoBDs), aiding influenza A virus (IAV) spread and immunity. Haloperidol inhibits this process, impacting viral propagation.
Area of Science:
- Cell Biology
- Virology
- Immunology
Background:
- Apoptosis involves cell disassembly into apoptotic bodies (ApoBDs), but their function is unclear.
- Monocytes undergoing apoptosis generate beaded apoptopodia that fragment into numerous ApoBDs.
Purpose of the Study:
- To investigate the function of apoptotic monocyte disassembly.
- To explore the role of ApoBDs in influenza A virus (IAV) infection.
Main Methods:
- Utilized influenza A virus (IAV) infection as a model for studying monocyte apoptosis.
- Analyzed the contents of ApoBDs from IAV-infected monocytes.
- Investigated the effect of Haloperidol on monocyte cell disassembly and ApoBD-mediated viral propagation.
Main Results:
- ApoBDs from IAV-infected monocytes contained viral mRNA, protein, and virions.
- These ApoBDs facilitated viral propagation in vitro and in vivo.
- ApoBDs also induced a significant antiviral immune response.
- Haloperidol inhibited monocyte cell disassembly and impaired ApoBD-mediated viral propagation.
Conclusions:
- Apoptotic monocyte disassembly plays a previously unrecognized role in IAV pathogenesis.
- ApoBDs contribute to viral spread and modulate the immune response during IAV infection.
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