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Journal of Virology, October 2004, p. 10536-10542, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10536-10542.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 (HIV-1) Antigen Secretion by Latently Infected Resting CD4+ T Lymphocytes from HIV-1-Infected Individuals

Jean-Michel Fondere,1,{dagger} Gael Petitjean,1,{dagger} Marie-France Huguet,1 Sharon Lynn Salhi,2 Vincent Baillat,3 Anna Macura-Biegum,4 Pierre Becquart,5 Jacques Reynes,3 and Jean-Pierre Vendrell1,6*

Laboratoire de Virologie, Hôpital Lapeyronie,1 CNRS UMR 5160, Centre de Pharmacologie et Biotechnologie pour la Santé, Faculté de Pharmacie,2 Departement des Maladies Infectieuses et Tropicales, Hôpital Gui de Chauliac,3 Institut de Recherche pour le Developpement UR 36,5 INSERM U 475, Immunopathologie des Maladies Tumorales et Auto-immunes, Montpellier, France,6 Department of Clinical Immunology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland4

Received 30 January 2004/ Accepted 19 May 2004

In resting CD4+ T lymphocytes harboring human immunodeficiency virus type 1 (HIV-1), replication-competent virus persists in patients responding to highly active antiretroviral therapy (HAART). This small latent reservoir represents between 103 and 107 cells per patient. However, the efficiency of HIV-1 DNA-positive resting CD4+ T cells in converting to HIV-1-antigen-secreting cells (HIV-1-Ag-SCs) after in vitro CD4+-T-cell polyclonal stimulation has not been satisfactorily evaluated. By using an HIV-1-antigen enzyme-linked immunospot assay, 8 HIV-1-Ag-SCs per 106 CD4+ resting T cells were quantified in 25 patients with a plasma viral load of <20 copies/ml, whereas 379 were enumerated in 10 viremic patients. In parallel, 369 and 1,238 copies of HIV-1 DNA per 106 CD4+ T cells were enumerated in the two groups of patients, respectively. Only a minority of latently HIV-1 DNA-infected CD4+ T cells could be stimulated in vitro to become HIV-1-Ag-SCs, particularly in aviremic patients. The difference between the number of HIV-1 immunospots in viremic versus aviremic patients could be explained by HIV-1 unintegrated viral DNA that gave additional HIV-1-Ag-SCs after in vitro CD4+-T-cell polyclonal stimulation. The ELISPOT approach to targeting the HIV-1-Ag-SCs could be a useful method for identifying latently HIV-1-infected CD4+ T cells carrying replication-competent HIV-1 in patients responding to HAART.

* Corresponding author. Mailing address: Laboratoire de Virologie, Hôpital Lapeyronie, Avenue du Doyen Gaston Giraud, 34295 Montpellier, France. Phone: 33 467 338 340. Fax: 33 467 338 334. E-mail: jp-vendrell{at}chu-montpellier.fr.

{dagger} J.-M. Fondere and G. Petitjean contributed equally to this work.

Journal of Virology, October 2004, p. 10536-10542, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10536-10542.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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