Extensive apoptosis in lymphoid organs during primary SIV infection predicts rapid progression towards AIDS

• Published in: AIDS (London) Vol. 17; no. 11; pp. 1585 - 1596
• Main Authors: MONCEAUX, Valérie, ESTAQUIER, Jérome, FEVRIER, Michèle, CUMONT, Marie-Christine, RIVIERE, Yves, AUBERTIN, Anne-Marie, AMEISEN, Jean Claude, HURTREL, Bruno
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 25.07.2003
• Subjects: Acute Disease; AIDS/HIV; Animals; Apoptosis; Biological and medical sciences; Biomarkers - analysis; Cell Cycle; Cell Division; Disease Progression; Human viral diseases; Infectious diseases; Ki-67 Antigen - analysis; Lymph Nodes - pathology; Lymph Nodes - virology; Macaca mulatta; Medical sciences; Simian Acquired Immunodeficiency Syndrome - virology; Simian Immunodeficiency Virus - physiology; T-Lymphocytes, Cytotoxic - immunology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viremia; Virus Replication; Immunopathology; SIV; Prognosis; Primary infection; Retroviridae; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Lymphoid organ; Viral disease; Evolution; Predictive factor; Simian immunodeficiency virus; Apoptosis
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-200307250-00002

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. 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. 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. 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.