Phagocytosis is crucial for triggering host defenses against invading pathogens in animals. However, the receptors on phagocyte surface required for phagocytosis of virus have not been extensively explored. This study demonstrated that white spot syndrome virus (WSSV), a major pathogen of shrimp, could be engulfed but not digested by Drosophila S2 cells, indicating that the virus was not recognized and taken up by a pathway that was silent and would not activate the phagosome maturation and digestion pathway. The results showed that the activation of receptors on S2 cell surface by lipopolysaccharide or peptidoglycan resulted in the phagocytosis of S2 cells against WSSV virions. Gene expression profiles revealed that the dally-mediated Wnt signaling pathway was involved in S2 phagocytosis. Further data showed that the Wnt signaling pathway played an essential role in phagocytosis. Therefore, our study contributed novel insight into the molecular mechanism of phagocytosis in animals.