1887

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)-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.

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2009-04-01
2020-09-26
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