HIV replication in CD4+ T cells of HIV-infected individuals is regulated by a balance between the viral suppressive effects of endogenous beta-chemokines and the viral inductive effects of other endogenous cytokines.
This study demonstrates that the beta-chemokines macrophage inflammatory proteins 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta) and, RANTES (regulated on activation, normally T-cell expressed and secreted) inhibit human immunodeficiency virus (HIV) replication in anti-CD3 or recall antigen-stimulated peripheral blood mononuclear cells (PBMCs) of asymptomatic HIV-infected subjects. Significant levels of beta-chemokines were produced by both CD4+ and CD8+ PBMC subsets from HIV-infected individuals. Neutralization of endogenous MIP-1 alpha, MIP-1 beta, and RANTES did not rescue HIV replication in cultures to which greater than 10% CD8+ T cells had been added, indicating that the HIV suppressor activity of CD8+ T cells cannot be explained entirely by the beta-chemokines. However, significant enhancement of viral replication was observed upon neutralization of endogenous beta-chemokines in CD8-depleted or CD4+ PBMCs from most donors, particularly in cultures with low inducible levels of HIV production. In contrast, certain endogenous proinflammatory cytokines induced HIV replication in these same cells. These data suggest that the levels of HIV replication in CD4+ PBMC reflect the balance of the opposing effects of endogenous suppressive factors, such as the beta-chemokines, and HIV-inducing cytokines, such as tumor necrosis factor alpha and interleukin 1 beta.
Kinter
A L
AL
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1576, USA.
Ostrowski
M
M
Goletti
D
D
Oliva
A
A
Weissman
D
D
Gantt
K
K
Hardy
E
E
Jackson
R
R
Ehler
L
L
Fauci
A S
AS
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis* / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007700:Kinetics; D008212:Lymphocyte Depletion; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013745:Tetanus Toxoid / Q000494:pharmacology; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D011994:Recombinant Proteins; D013745:Tetanus Toxoid