Extensive apoptosis in lymphoid organs during primary SIV infection predicts rapid progression towards AIDS
作者:
Valérie Monceaux,
Jérôme Estaquier,
Michèle Février,
Marie-Christine Cumont,
Yves Rivière,
Anne-Marie Aubertin,
Jean Ameisen,
Bruno Hurtrel,
期刊:
AIDS
(OVID Available online 2003)
卷期:
Volume 17,
issue 11
页码: 1585-1596
ISSN:0269-9370
年代: 2003
出版商: OVID
关键词: AIDS;apoptosis;primary infection;SIV
数据来源: OVID
摘要:
Objective:The acute phase of HIV and SIV infections leads to a host/virus equilibrium, and accumulating evidence suggests that this early phase dictates further progression towards AIDS. To gain insight into the early events that determine rapid disease progression, we performed a longitudinal study in the SIV rhesus macaque model, allowing an in-depth analysis of the primary stage of infection.Methods:We assessed viral replication (quantification of replicating and infected cells in lymph nodes, plasma viral load), immune response (cytotoxic T lymphocyte, antibody, proliferative responses), apoptosis and cycling cells (Ki-67 labelling) on lymph nodes and blood in nine rhesus macaques infected with the pathogenic SIVmac251 isolate.Results:Six primates remained asymptomatic during the one year follow-up period of the study, whereas three developed AIDS within 5–6 months. During the first 2 weeks of infection, peak numbers of apoptotic cells in the lymph node T-cell areas were significantly higher in the three future rapid progressors than in the six future slow progressors, and were correlated with subsequent viraemia levels measured 6 months after infection. The numbers of infected or cycling cells in the same lymph node T-cell areas, however, only became significantly different in future rapid and slow progressors 8 weeks after infection, at the end of the primary phase.Conclusion:Our findings identified extensive apoptosis induction in peripheral lymphoid organs as an early and predictive event that may play a crucial role in impairing the capacity of the immune system to control viral replication and progression towards disease.
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