Open AccessAcute-phase CD4+ T-cell proliferation and CD152 upregulation predict set-point virus replication in vaccinated simian–human immunodeficiency virus strain 89.6p-infected macaques
Author(s) -
Gerrit Koopman,
Daniëlla Mortier,
Sam Hofman,
Marguerite Koutsoukos,
Willy Bogers,
Britta Wahrén,
Gérald Voss,
Jonathan L. Heeney
Publication year - 2009
Publication title -
journal of general virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.55
H-Index - 167
eISSN - 1465-2099
pISSN - 0022-1317
DOI - 10.1099/vir.2008.006148-0
Subject(s) - simian immunodeficiency virus , virology , biology , virus , cd8 , viral load , viral replication , t cell , immunology , cytotoxic t cell , lentivirus , immune system , viral disease , in vitro , genetics
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.