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

J Gen Virol. 2009 Apr;90(Pt 4):915-926. doi: 10.1099/vir.2008.006148-0. Epub 2009 Feb 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / administration & dosage*
  • Acute Disease
  • Animals
  • Antigens, CD / metabolism*
  • CD4-Positive T-Lymphocytes / immunology*
  • CTLA-4 Antigen
  • HIV / immunology
  • HIV / pathogenicity
  • HIV Infections* / immunology
  • HIV Infections* / prevention & control
  • HIV Infections* / virology
  • Humans
  • Interferon-gamma / metabolism
  • Lymphocyte Activation / immunology
  • Macaca
  • SAIDS Vaccines / administration & dosage*
  • Simian Acquired Immunodeficiency Syndrome* / immunology
  • Simian Acquired Immunodeficiency Syndrome* / prevention & control
  • Simian Acquired Immunodeficiency Syndrome* / virology
  • Simian Immunodeficiency Virus / immunology
  • Simian Immunodeficiency Virus / pathogenicity
  • Up-Regulation*
  • Virus Replication*

Substances

  • AIDS Vaccines
  • Antigens, CD
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • SAIDS Vaccines
  • Interferon-gamma