title: Disease progression in macaques with low SIV replication levels: on the relevance of TREC counts.
abstract: BACKGROUND
  An attenuated immunodeficiency virus has been long considered innocuous. Nevertheless, converging data suggest that low levels of viral replication can still provoke AIDS. Pathogenesis of these attenuated infections is not understood.
  
  
  OBJECTIVE
  To determine the pathogenicity of a long-term attenuated infection and to delineate T-cell dynamics during such an infection.
  
  
  METHODS
  This is a cross-sectional study of 12 rhesus macaques infected with SIV Delta nef for 8 years. We evaluated apoptosis (annexin V), activation (HLA-DR, Ki67), and newly generated T cells (TCR excision circle: TREC).
  
  
  RESULTS
  Infection with SIV Delta nef induced pathological CD4 T-cell depletion after 8 years of infection. Virus replication and CD8 T-cell activation positively correlated with the rate of disease progression. The frequency of TREC within CD8+CD45RA+ cells increased in SIV Delta nef-infected animals compared to age-matched non-infected controls. Moreover, in the cohort of infected animals, TREC+CD45RA+CD4+ T-cell counts correlated strongly with non-progression to AIDS. The animal with the lowest rate of disease progression exhibited a 115-fold increase in TREC+CD45RA+CD4+ T-cell counts compared to age-matched non-infected controls. In contrast, the animal showing the fastest rate of progression to AIDS displayed 600-fold lower TREC+CD45RA+CD4+ T-cell counts compared to age-matched non-infected controls.
  
  
  CONCLUSIONS
  Our results suggest that the thymus plays a major role in the pathogenesis of an attenuated SIV infection and that a sustained thymic output could maintain CD4 T-cell homeostasis in the context of low viral loads.
authors.affiliation: Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, Paris, France. rhotsong@ucla.edu
authors.forename: Raphaël
authors.initials: R
authors.lastname: Ho Tsong Fang
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Khatissian
authors.forename: Valérie
authors.initials: V
authors.lastname: Monceaux
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Cumont
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Beq
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Ameisen
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Aubertin
authors.forename: Nicole
authors.initials: N
authors.lastname: Israël
authors.forename: Jérôme
authors.initials: J
authors.lastname: Estaquier
authors.forename: Bruno
authors.initials: B
authors.lastname: Hurtrel
mesh_terms: D000818:Animals; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes; D049109:Cell Proliferation; D018450:Disease Progression; D015693:Gene Products, nef; D015329:Gene Rearrangement, T-Lymphocyte; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication
chemical_list: D015693:Gene Products, nef; D017493:Leukocyte Common Antigens