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

• Published in: Journal of general virology 2009-04, Vol.90 (4), p.915-926, Article 915
• Main Authors: Koopman, Gerrit, Mortier, Daniella, Hofman, Sam, Koutsoukos, Marguerite, Bogers, Willy M. J. M, Wahren, Britta, Voss, Gerald, Heeney, Jonathan L
• Format: Article
• Language: English
• Subjects: Acute Disease; AIDS Vaccines - administration & dosage; Animals; Antigens, CD - metabolism; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CTLA-4 Antigen; Fundamental and applied biological sciences. Psychology; HIV - immunology; HIV - pathogenicity; HIV Infections - immunology; HIV Infections - prevention & control; HIV Infections - virology; Human immunodeficiency virus; Humans; Interferon-gamma - metabolism; Lymphocyte Activation - immunology; Macaca; Macaca mulatta; Medicin och hälsovetenskap; Microbiology; Miscellaneous; SAIDS Vaccines - administration & dosage; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian Acquired Immunodeficiency Syndrome - virology; Simian immunodeficiency virus; Simian Immunodeficiency Virus - immunology; Simian Immunodeficiency Virus - pathogenicity; Simian/human immunodeficiency virus; Up-Regulation; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Virology; Virus Replication
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.2008.006148-0

1 Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands 2 GlaxoSmithKline Biologicals, Rixensart, Belgium 3 Swedish Institute for Infectious Disease Control, Karolinska Institutet, Stockholm, Sweden 4 Department of Veterinary Medicine, University of Cambridge, UK Correspondence Gerrit Koopman koopman{at}bprc.nl 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.