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


CONCLUSIONS
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.
Monceaux
Valérie
V
Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, CNRS URA 1930, 28 rue du Docteur Roux, 75724 Paris, France.
Estaquier
Jérôme
J
Février
Michèle
M
Cumont
Marie-Christine
MC
Rivière
Yves
Y
Aubertin
Anne-Marie
AM
Ameisen
Jean Claude
JC
Hurtrel
Bruno
B
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D002453:Cell Cycle; D002455:Cell Division; D018450:Disease Progression; D019394:Ki-67 Antigen / Q000032:analysis; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014766:Viremia; D014779:Virus Replication
D015415:Biomarkers; D019394:Ki-67 Antigen