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Direct detection of apoptotic cells in peripheral blood from highly pathogenic SHIV-inoculated monkey
1AIDS Research Center, Division of Experimental Animal Research, Division of Biosafety Control and Research, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, 162-8640, Japan.
Abstract:
Apoptosis in peripheral blood leukocytes (PBL) has been estimated by the enhancement of spontaneous apoptosis after in vitro culture, because apoptotic cells have not been observed directly in freshly isolated PBL in the course of HIV/AIDS. In monkeys infected with a highly pathogenic simian/human immunodeficiency virus (SHIV), which corresponds to rapid progressors of HIV infection, a high frequency of apoptotic cells was directly detected in fresh PBL by electron-microscopic studies. Peripheral blood apoptosis transiently occurred after intense plasma viremia, and peaking at 3 weeks postinfection; occurrence was not limited specifically to lymphocytes, but also occurred in other types of leukocytes. Apoptosis in peripheral lymph nodes was also detected following intense plasma viremia. However, the in vivo apoptosis was not detected in nonpathogenic SHIV-infected monkeys that showed no cell loss. Thus, we directly showed the apoptosis of PBL, which might be associated with pathogenic SHIV produced during the time of plasma viremia.
Insights
Directly detecting apoptosis in peripheral blood leukocytes (PBL) of monkeys infected with pathogenic simian/human immunodeficiency virus (SHIV) revealed transient cell death during peak viremia, unlike in nonpathogenic infections.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Apoptosis in peripheral blood leukocytes (PBL) is difficult to detect directly in HIV/AIDS patients.
- Previous estimations relied on in vitro culture, potentially altering natural apoptosis rates.
Purpose of the Study:
- To directly detect and characterize in vivo apoptosis of PBL in a simian immunodeficiency virus (SHIV) infection model.
- To investigate the association between pathogenic SHIV infection, viremia, and PBL apoptosis.
Main Methods:
- Electron-microscopic studies of PBL from monkeys infected with pathogenic or nonpathogenic SHIV.
- Monitoring of plasma viremia and assessment of apoptosis in PBL and lymph nodes.
Main Results:
- A high frequency of apoptotic cells was directly detected in fresh PBL of monkeys infected with pathogenic SHIV.
- Peripheral blood apoptosis occurred transiently after intense plasma viremia, peaking at 3 weeks postinfection.
- Apoptosis was observed in various leukocyte types and in peripheral lymph nodes, but not in nonpathogenic SHIV-infected monkeys.
Conclusions:
- Pathogenic SHIV infection directly induces apoptosis in PBL in vivo.
- This in vivo apoptosis is transient and linked to periods of high plasma viremia.
- The findings suggest a direct role for pathogenic SHIV in inducing leukocyte apoptosis during infection.