title: Acute-phase CD4+ T-cell proliferation and CD152 upregulation predict set-point virus replication in vaccinated simian-human immunodeficiency virus strain 89.6p-infected macaques.
abstract: Human immunodeficiency virus (HIV) infection in humans and simian immunodeficiency virus (SIV) infection in macaques are accompanied by a combined early loss of CCR5 (CD195)-expressing CD4(+) memory T cells, loss of T-helper function and T-cell hyperactivation, which have all been associated with development of high virus load and disease progression. Here, a cohort of vaccinated simian-human immunodeficiency virus strain 89.6p (SHIV(89.6p))-infected rhesus macaques, where preferential depletion of these memory T-cell subsets does not take place and CD4(+) T cells are relatively well maintained, was used to study the role of hyperactivation as an independent factor in the establishment of set-point virus load. In the acute phase of the infection, a transient loss of CD4(+) T cells, as well as strong increases in expression of proliferation and activation markers on CD4(+) and CD8(+) T cells, together with CD152 expression on CD4(+) T cells, were observed. Peak expression levels of these markers on CD4(+) T cells, but not on CD8(+) T cells, were correlated with high virus replication in the chronic phase of the infection. In addition, the peak expression level of these markers was correlated inversely with acute-phase, but not chronic-phase, HIV/SIV-specific gamma interferon responses. These data highlight a central role for an acute but transient CD4 decrease, as well as CD4(+) T-cell activation, as independent factors for prediction of set-point levels of virus replication.
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Koopman
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Daniella
authors.initials: D
authors.lastname: Mortier
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Sam
authors.initials: S
authors.lastname: Hofman
authors.affiliation: GlaxoSmithKline Biologicals, Rixensart, Belgium.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Koutsoukos
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Willy M J M
authors.initials: WMJM
authors.lastname: Bogers
authors.affiliation: Swedish Institute for Infectious Disease Control, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Britta
authors.initials: B
authors.lastname: Wahren
authors.affiliation: GlaxoSmithKline Biologicals, Rixensart, Belgium.
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, UK.|Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage*; D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D006678:HIV / Q000276:immunology / Q000472:pathogenicity; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008251:Macaca; D018449:SAIDS Vaccines / Q000008:administration & dosage*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D015854:Up-Regulation; D014779:Virus Replication
chemical_list: D016915:AIDS Vaccines; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018449:SAIDS Vaccines; D007371:Interferon-gamma