Human immunodeficiency virus type 1 DNA synthesis, integration, and efficient viral replication in growth-arrested T cells.

ABSTRACT Elite suppressors (ES) are untreated human immunodeficiency virus type 1 (HIV-1)-infected patients who maintain viral loads of <50 copies/ml. The mechanisms involved in this control of viral replication remain unclear. Prior studies suggested that these patients, as well as long-term nonprogressors, are infected with defective HIV-1 variants. Other reports have shown that the HLA-B*27 and -B*57 alleles are overrepresented in these patients, suggesting that host factors play a role in the control of viral replication. In order to distinguish between these hypotheses, we studied differences in viral isolates and immune responses of an HIV-1 transmission pair. While both patients are HLA-B*57 positive, the transmitter progressed to AIDS, whereas the recipient, who is also HLA-B*27 positive, is an ES. Isolates from both patients were replication competent and contained the T242N escape mutation in Gag, which is known to decrease viral fitness. While the acquisition of compensatory mutations occurred in isolates from the progressor, a superior HIV-specific CD8+ T-cell response in the ES appears to have prevented viral replication and thus the evolution toward a more fit variant. In addition, CD8+ T cells in the ES have selected for a rare mutation in an immunodominant HLA-B*27-restricted Gag epitope, which also has a negative impact on fitness. The results strongly suggest that through direct and indirect mechanisms, CD8+ T cells in some ES control HIV-1 isolates are capable of causing profound immunosuppression.

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Resistance of chimpanzee T cells to human immunodeficiency virus type 1 Tat-enhanced oxidative stress and apoptosis.

Journal of Virology ◽

10.1128/jvi.70.9.6502-6507.1996 ◽

1996 ◽

Vol 70 (9) ◽

pp. 6502-6507 ◽

Cited By ~ 31

Author(s):

A Ehret ◽

M O Westendorp ◽

I Herr ◽

K M Debatin ◽

J L Heeney ◽

...

Keyword(s):

Oxidative Stress ◽

Human Immunodeficiency Virus ◽

T Cells ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Immunodeficiency Virus

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Increased Density of Human Immunodeficiency Virus Type 1 Coreceptors CCR5 and CXCR4 on the Surfaces of CD4+ T Cells and Monocytes of Patients with Schistosoma mansoni Infection

Infection and Immunity ◽

10.1128/iai.71.11.6668-6671.2003 ◽

2003 ◽

Vol 71 (11) ◽

pp. 6668-6671 ◽

Cited By ~ 58

Author(s):

W. Evan Secor ◽

Amil Shah ◽

Pauline M. N. Mwinzi ◽

Bryson A. Ndenga ◽

Caroline O. Watta ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Cell Surface ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Peripheral Blood ◽

Chemokine Receptors ◽

Blood Samples ◽

Immunodeficiency Virus

ABSTRACT Distribution of chemokine receptors CCR5 and CXCR4, which are also coreceptors for human immunodeficiency virus type 1 invasion of cells, was measured on the surfaces of CD4+ T cells and monocytes in peripheral blood samples from a group of Kenyan car washers. Patients with active schistosomiasis displayed higher cell surface densities of these receptors than did cured schistosomiasis patients.

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Hemofiltrate CC Chemokine 1[9-74] Causes Effective Internalization of CCR5 and Is a Potent Inhibitor of R5-Tropic Human Immunodeficiency Virus Type 1 Strains in Primary T Cells and Macrophages

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.4.982-990.2002 ◽

2002 ◽

Vol 46 (4) ◽

pp. 982-990 ◽

Cited By ~ 29

Author(s):

Jan Münch ◽

Ludger Ständker ◽

Stefan Pöhlmann ◽

Frédéric Baribaud ◽

Armin Papkalla ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Proteolytic Processing ◽

Cell Surface Expression ◽

Cc Chemokine ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Proteolytic processing of the abundant plasmatic human CC chemokine 1 (HCC-1) generates a truncated form, HCC-1[9-74], which is a potent agonist of CCR1, CCR3, and CCR5; promotes calcium influx and chemotaxis of T lymphoblasts, monocytes, and eosinophils; and inhibits infection by CCR5-tropic human immunodeficiency virus type 1 (HIV-1) isolates. In the present study we demonstrate that HCC-1[9-74] interacts with the second external loop of CCR5 and inhibits replication of CCR5-tropic HIV-1 strains in both primary T cells and monocyte-derived macrophages. Low concentrations of the chemokine, however, frequently enhanced the replication of CCR5-tropic HIV-1 isolates but not the replication of X4-tropic HIV-1 isolates. Only HCC-1[9-74] and HCC-1[10-74], but not other HCC-1 length variants, displayed potent anti-HIV-1 activities. Fluorescence-activated cell sorter analysis revealed that HCC-1[9-74] caused up to 75% down-regulation of CCR5 cell surface expression, whereas RANTES (regulated on activation, normal T-cell expressed and secreted) achieved a reduction of only about 40%. Studies performed with green fluorescent protein-tagged CCR5 confirmed that both HCC-1[9-74] and RANTES, but not full-length HCC-1, mediated specific internalization of the CCR5 HIV-1 entry cofactor. Our results demonstrate that the interaction with HCC-1[9-74] causes effective intracellular sequestration of CCR5, but they also indicate that the effect of HCC-1[9-74] on viral replication is subject to marked cell donor- and HIV-1 isolate-dependent variations.

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Nef Induces Multiple Genes Involved in Cholesterol Synthesis and Uptake in Human Immunodeficiency Virus Type 1-Infected T Cells

Journal of Virology ◽

10.1128/jvi.79.15.10053-10058.2005 ◽

2005 ◽

Vol 79 (15) ◽

pp. 10053-10058 ◽

Cited By ~ 64

Author(s):

Angélique B. van ′t Wout ◽

J. Victor Swain ◽

Michael Schindler ◽

Ushnal Rao ◽

Melissa S. Pathmajeyan ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cholesterol Synthesis ◽

Cholesterol Biosynthesis ◽

Acetate Incorporation ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Several recent reports indicate that cholesterol might play an important role in human immunodeficiency virus type 1 (HIV-1) replication. We investigated the effects of HIV-1 infection on cholesterol biosynthesis and uptake using microarrays. HIV-1 increased gene expression of cholesterol genes in both transformed T-cell lines and primary CD4+ T cells. Consistent with our microarray data, 14C-labeled mevalonate and acetate incorporation was increased in HIV-1-infected cells. Our data also demonstrate that changes in cholesterol biosynthesis and uptake are only observed in the presence of functional Nef, suggesting that increased cholesterol synthesis may contribute to Nef-mediated enhancement of virion infectivity and viral replication.

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