Role of phosphatidylserine exposure and sugar chain desialylation at the surface of influenza virus-infected cells in efficient phagocytosis by macrophages.
HeLa cells infected with influenza A virus undergo typical caspase-dependent apoptosis and are efficiently phagocytosed by mouse peritoneal macrophages in a manner mediated by the membrane phospholipid phosphatidylserine, which is translocated to the surface of virus-infected cells during apoptosis. However, the extent of phagocytosis is not always parallel with the level of phosphatidylserine externalization. Here we examined the involvement of influenza virus neuraminidase (NA) in efficient phagocytosis of virus-infected cells. HeLa cells infected with an influenza virus strain expressing temperature-sensitive NA underwent apoptosis and produced viral proteins, including the defective NA, at a non-permissive temperature to almost the same extent as cells infected with the wild-type virus. The cells were, however, phagocytosed by macrophages with reduced efficiency. In addition, phagocytosis of cells infected with the wild-type virus was severely inhibited when the cells had been maintained in the presence of the NA inhibitor zanamivir. On the other hand, the binding of sialic acid-recognizing lectins to the cell surface declined after infection with the wild-type virus. The decrease in the extent of lectin binding was greatly attenuated when cells were infected with the mutant virus or when wild-type virus-infected cells were maintained in the presence of zanamivir. These results indicate that sugar chains are desialylated by NA at the surface of virus-infected cells. We conclude that the presence of both phosphatidylserine and asialoglycomoieties on the cell surface is required for efficient phagocytosis of influenza virus-infected cells by macrophages.
Watanabe
Yuichi
Y
Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-0934, Japan.
Shiratsuchi
Akiko
A
Shimizu
Kazufumi
K
Takizawa
Takenori
T
Nakanishi
Yoshinobu
Y
D006367:HeLa Cells; D006801:Humans; D009980:Influenza A virus / Q000235:genetics; D007251:Influenza, Human / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000502:physiology*; D013499:Surface Properties
D010718:Phosphatidylserines; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid