title: CD4+ CCR5+ T-cell dynamics during simian immunodeficiency virus infection of Chinese rhesus macaques.
abstract: Simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) provides a reliable model to study the relationship between lentivirus replication, cellular immune responses, and CD4+ T-cell dynamics. Here we investigated, using SIVmac251-infected RMs of a Chinese genetic background (which experience a slower disease progression than Indian RMs), the dynamics of CD4+ CCR5+ T cells, as this subset of memory/activated CD4+ T cells is both a preferential target of virus replication and a marker of immune activation. As expected, we observed that the number of circulating CD4+ CCR5+ T cells decreases transiently at the time of peak viremia. However, at 60 days postinfection, i.e., when set-point viremia is established, the level of CD4+ CCR5+ T cells was increased compared to the baseline level. Interestingly, this increase correlated with faster disease progression, higher plasma viremia, and early loss of CD4+ T-cell function, as measured by CD4+ T-cell count, the fraction of memory CD4+ T cells, and the recall response to purified protein derivative. Taken together, these data show a key difference between the dynamics of the CD4+ CCR5+ T-cell pool (and its relationship with disease progression) in Chinese RMs and those described in previous reports for Indian SIVmac251-infected RMs. As the SIV-associated changes in the CD4+ CCR5+ T-cell pool reflect the opposing forces of SIV replication (which reduces this cellular pool) and immune activation (which increases it), our data suggest that in SIV-infected Chinese RMs the impact of immune activation is more prominent than that of virus replication in determining the size of the pool of CD4+ CCR5+ T cells in the periphery. As progression of HIV infection in humans also is associated with a relative expansion of the level of CD4+ CCR5+ T cells, we propose that SIV infection of Chinese RMs is a very valuable and important animal model for understanding the pathogenesis of human immunodeficiency virus infection.
authors: Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France.
authors: V
authors: V
authors: Monceaux
authors: L
authors: L
authors: Viollet
authors: F
authors: F
authors: Petit
authors: M C
authors: MC
authors: Cumont
authors: G R
authors: GR
authors: Kaufmann
authors: A M
authors: AM
authors: Aubertin
authors: B
authors: B
authors: Hurtrel
authors: G
authors: G
authors: Silvestri
authors: J
authors: J
authors: Estaquier
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002681:China; D004195:Disease Models, Animal; D018450:Disease Progression; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D014779:Virus Replication
chemical_list: D012367:RNA, Viral; D019713:Receptors, CCR5