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AIDS. 2003 Jul 25;17(11):1585-96.

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

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1
Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, CNRS URA 1930, 28 rue du Docteur Roux, 75724 Paris, France.

Abstract

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.

[Indexed for MEDLINE]

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