Human immunodeficiency virus type 1 (HIV-1) antigen secretion by latently infected resting CD4+ T lymphocytes from HIV-1-infected individuals.
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 10(3) and 10(7) 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 10(6) 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 10(6) 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.
Fondere
Jean-Michel
JM
Laboratoire de Virologie, Hôpital Lapeyronie, Avenue du Doyen Gaston Giraud, 34295 Montpellier, France.
Petitjean
Gael
G
Huguet
Marie-France
MF
Salhi
Sharon Lynn
SL
Baillat
Vincent
V
Macura-Biegun
Anna
A
Becquart
Pierre
P
Reynes
Jacques
J
Vendrell
Jean-Pierre
JP
Macura-Biegum
Anna
A
D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D015488:HIV Antigens / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D013997:Time Factors; D019562:Viral Load; D014766:Viremia; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
D004279:DNA, Viral; D015488:HIV Antigens