Abstract
This study demonstrates that the β-chemokines macrophage inflammatory proteins 1α and 1β (MIP-1α and MIP-1β) 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 (PB-MCs) of asymptomatic HIV-infected subjects. Significant levels of β-chemokines were produced by both CD4+ and CD8+ PBMC subsets from HIV-infected individuals. Neutralization of endogenous MIP-1α, MIP-1β, 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 β-chemokines. However, significant enhancement of viral replication was observed upon neutralization of endogenous β-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 β-chemokines, and HIV-inducing cytokines, such as tumor necrosis factor α and interleukin 1β.
| Original language | English |
|---|---|
| Pages (from-to) | 14076-14081 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 93 |
| Issue number | 24 |
| Publication status | Published - Nov 26 1996 |
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Keywords
- Proinflammatory
- Regulation
ASJC Scopus subject areas
- General
- Genetics
Cite this
HIV replication in CD4+ T cells of HIV-infected individuals is regulated by a balance between the viral suppressive effects of endogenous β-chemokines and the viral inductive effects of other endogenous cytokines. / Kinter, Audrey L.; Ostrowski, Mario; Goletti, Delia; Oliva, Alessandra; Weissman, Drew; Gantt, Kira; Hardy, Elena; Jackson, Robert; Ehler, Linda; Fauci, Anthony S.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 24, 26.11.1996, p. 14076-14081.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - HIV replication in CD4+ T cells of HIV-infected individuals is regulated by a balance between the viral suppressive effects of endogenous β-chemokines and the viral inductive effects of other endogenous cytokines
AU - Kinter, Audrey L.
AU - Ostrowski, Mario
AU - Goletti, Delia
AU - Oliva, Alessandra
AU - Weissman, Drew
AU - Gantt, Kira
AU - Hardy, Elena
AU - Jackson, Robert
AU - Ehler, Linda
AU - Fauci, Anthony S.
PY - 1996/11/26
Y1 - 1996/11/26
N2 - This study demonstrates that the β-chemokines macrophage inflammatory proteins 1α and 1β (MIP-1α and MIP-1β) 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 (PB-MCs) of asymptomatic HIV-infected subjects. Significant levels of β-chemokines were produced by both CD4+ and CD8+ PBMC subsets from HIV-infected individuals. Neutralization of endogenous MIP-1α, MIP-1β, 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 β-chemokines. However, significant enhancement of viral replication was observed upon neutralization of endogenous β-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 β-chemokines, and HIV-inducing cytokines, such as tumor necrosis factor α and interleukin 1β.
AB - This study demonstrates that the β-chemokines macrophage inflammatory proteins 1α and 1β (MIP-1α and MIP-1β) 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 (PB-MCs) of asymptomatic HIV-infected subjects. Significant levels of β-chemokines were produced by both CD4+ and CD8+ PBMC subsets from HIV-infected individuals. Neutralization of endogenous MIP-1α, MIP-1β, 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 β-chemokines. However, significant enhancement of viral replication was observed upon neutralization of endogenous β-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 β-chemokines, and HIV-inducing cytokines, such as tumor necrosis factor α and interleukin 1β.
KW - Proinflammatory
KW - Regulation
UR - http://www.scopus.com/inward/record.url?scp=0030465244&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030465244&partnerID=8YFLogxK
M3 - Article
C2 - 8943063
AN - SCOPUS:0030465244
VL - 93
SP - 14076
EP - 14081
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 24
ER -