We investigated whether phagocytosis participates in the protection of insects from
viral infection using the natural host-virus interaction between Drosophila melanogaster and Drosophila C virus (DCV). Drosophila S2 cells were induced to undergo apoptotic cell death upon DCV
infection. However, UV-inactivated virus was unable to cause apoptosis, indicating the need for productive
infection for apoptosis induction. S2 cells became susceptible to phagocytosis by hemocyte-derived l(2)mbn cells after
viral infection, and the presence of phagocytes in S2 cell cultures reduced viral proliferation. Phagocytosis depended, in part, on
caspase activity in S2 cells, as well as the engulfment receptors Draper and
integrin βν in phagocytes. To validate the in vivo situation, adult flies were abdominally infected with DCV, followed by the analysis of fly death and viral growth. DCV
infection killed flies in a dose-responding manner, and the activation of
effector caspases was evident, as revealed by the cleavage of a target
protein ectopically expressed in flies. Furthermore, hemocytes isolated from infected flies contained DCV-infected cells, and preinjection of
latex beads to inhibit the phagocytic activity of hemocytes accelerated fly death after
viral infection. Likewise, viral virulence was exaggerated in flies lacking the engulfment receptors, and was accompanied by the augmented proliferation of virus. Finally, phagocytosis of DCV-infected cells in vitro was inhibited by
phosphatidylserine-containing
liposome, and virus-infected flies died early when a
phosphatidylserine-
binding protein was ectopically expressed. Collectively, our study demonstrates that the apoptosis-dependent,
phosphatidylserine-mediated phagocytosis of virus-infected cells plays an important role in innate immune responses against
viral infection in Drosophila.