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Journal of Virology, April 2000, p. 3399-3403, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Virus Clearance through Apoptosis-Dependent Phagocytosis of Influenza A Virus-Infected Cells by Macrophages

Ippei Fujimoto,1 Jiehong Pan,2 Takenori Takizawa,3 and Yoshinobu Nakanishi1,*

Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Ishikawa 920-0934,1 Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa 920-0265,2 and Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392,3 Japan

Received 20 October 1999/Accepted 4 January 2000

Some cultured cell lines undergo typical apoptosis upon infection with influenza virus. However, the release of replicated virus into the culture medium does not change when apoptosis is inhibited. Since apoptotic cells are heterophagically eliminated at early stages of the apoptosis pathway, we anticipated that the coexistence of phagocytic cells with virus-infected cells affects the extent of virus growth. When influenza A virus-infected HeLa cells were mixed with activated mouse peritoneal macrophages, efficient phagocytosis, which was abrogated in the presence of a caspase inhibitor, occurred. At the same time, the release of virus into the culture medium was completely inhibited, and this required direct contact between virus-infected cells and macrophages. Furthermore, an immunoelectron microscopic analysis detected influenza virus particles associated with phagosome-like structures within macrophages. These results indicate that apoptosis-dependent phagocytosis of virus-infected cells may lead to direct elimination of the pathogen.

* Corresponding author. Mailing address: Graduate School of Natural Science and Technology, Kanazawa University, Takara-machi, Kanazawa, Ishikawa 920-0934, Japan. Phone: 81-76-234-4481. Fax: 81-76-234-4480. E-mail: nakanaka{at}kenroku.kanazawa-u.ac.jp.

Journal of Virology, April 2000, p. 3399-3403, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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