Apoptosis and the clearance of apoptotic cells are essential to maintain physiological homeostasis.
Our previous work identified a series of protein regulators that govern the efficient dismantling of apoptotic cells into large EVs known apoptotic bodies (ApoBDs). These ApoBDs can communicate phagocytes through “find-me” and “goodbye” signals, and receptor-mediated interactions, such as phosphatidylserine-binding. Notably, we demonstrated that apoptotic cell disassembly plays a key role in host-pathogen interactions whereby Influenza A virus (IAV) and SARS-COV-2 viruses can induce fragmentation, resulting in ApoBDs capable of propagating viral infection in vitro and in vivo. Unexpectedly, recent work examining the mechanism of ApoBD-mediated viral transfer revealed that, in SARS-CoV-2, propagation of infection is efferocytosis-dependent, indicating that the virus can escape phagolysosome-mediated neutralization. However, if this mechanism is unique to SARS-COV-2 or is conserved across other respiratory viruses remains unknown.
Here, we employed FACs-based isolation to collect “engulfing” and “non-engulfing” phagocytes following co-incubation with ApoBDs generated during IAV viral infection. Through confocal microscopy and flow cytometry, we observed that “engulfing” phagocytes exhibited a significant enrichment of IAV proteins compared to “non-engulfing” phagocytes, suggesting that IAV propagation may also be efferocytosis-dependent. Importantly, these data highlight that efferocytosis of IAV-infected apoptotic material is not always abortive. To investigate how IAV escapes phagolysosomal neutralization, we developed a pharmacological screening approach using commercially available antivirals. Overall, these findings identify a novel mechanism of IAV infection mediated by ApoBDs and enhance our understanding of the role of ApoBDs and dying cell clearance in host-pathogen interactions.