Chemokine/CD4 receptor density ratios correlate with HIV replication in lymph node and peripheral blood of HIV-infected individuals

M. A. Nokta, X. D. Li, Joan Nichols, M. Mallen, A. Pou, D. Asmuth, R. B. Pollard

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Objectives: Lymphoid tissue is a major reservoir for virus replication in HIV-infected subjects. The relationship of CCR5 and CXCR4 coreceptor density and HIV replication in peripheral blood mononuclear cells (PBMC) and lymph node (LN) mononuclear cells (LNMC) of HIV-infected subjects was examined. Methods: PBMC and cervical LNMC from 12 HIV-infected patients were examined for virological and immunological parameters including chemokine receptor density, HIV plasma and cellular viral load, coreceptor usage and CD38/HLA-DR expression. Results: The number of CCR5 and CXCR4 molecules on CD4 lymphocytes in the LN were significantly higher than in PBMC. In contrast the number of CD4 molecules/ CD4 T cell was higher in PBMC than in LNMC. The CXCR4/CD4 and CCR5/CD4 ratios in the LN were significantly higher than in the PBMC. This was associated with a cellular viral load in the LN that was ∼110-fold higher than in PBMC. The absolute number of coreceptor molecules per cell did not correlate with the viral load. However, the CCR5/CD4 and CXCR4/CD4 ratios in the LN positively correlated with HIV cellular and plasma RNA. Characterization of the viral isolates suggested an association between clinical isolates using a distinct coreceptor and the upregulation of the corresponding chemokine receptor. Conclusions: The ratios of chemokine receptors to CD4 molecules in CD4 T cells from LN is higher than in PBMC and may account for the relative difference in cellular viral load in these compartments. Additionally, the coreceptor/CD4 ratios, particularly in the lymphoid tissue, were highly related to HIV replication.

Original languageEnglish (US)
Pages (from-to)161-169
Number of pages9
JournalAIDS
Volume15
Issue number2
DOIs
StatePublished - Jan 26 2001

Fingerprint

CD4 Antigens
Chemokine Receptors
Blood Cells
Lymph Nodes
HIV
Viral Load
Lymphoid Tissue
T-Lymphocytes
HLA-DR Antigens
Virus Replication
Up-Regulation
Lymphocytes
RNA

Keywords

  • CCR5
  • CD4
  • Chemokine receptors
  • CXCR4
  • HIV
  • Lymph nodes
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Chemokine/CD4 receptor density ratios correlate with HIV replication in lymph node and peripheral blood of HIV-infected individuals. / Nokta, M. A.; Li, X. D.; Nichols, Joan; Mallen, M.; Pou, A.; Asmuth, D.; Pollard, R. B.

In: AIDS, Vol. 15, No. 2, 26.01.2001, p. 161-169.

Research output: Contribution to journalArticle

Nokta, M. A. ; Li, X. D. ; Nichols, Joan ; Mallen, M. ; Pou, A. ; Asmuth, D. ; Pollard, R. B. / Chemokine/CD4 receptor density ratios correlate with HIV replication in lymph node and peripheral blood of HIV-infected individuals. In: AIDS. 2001 ; Vol. 15, No. 2. pp. 161-169.
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AU - Asmuth, D.

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AB - Objectives: Lymphoid tissue is a major reservoir for virus replication in HIV-infected subjects. The relationship of CCR5 and CXCR4 coreceptor density and HIV replication in peripheral blood mononuclear cells (PBMC) and lymph node (LN) mononuclear cells (LNMC) of HIV-infected subjects was examined. Methods: PBMC and cervical LNMC from 12 HIV-infected patients were examined for virological and immunological parameters including chemokine receptor density, HIV plasma and cellular viral load, coreceptor usage and CD38/HLA-DR expression. Results: The number of CCR5 and CXCR4 molecules on CD4 lymphocytes in the LN were significantly higher than in PBMC. In contrast the number of CD4 molecules/ CD4 T cell was higher in PBMC than in LNMC. The CXCR4/CD4 and CCR5/CD4 ratios in the LN were significantly higher than in the PBMC. This was associated with a cellular viral load in the LN that was ∼110-fold higher than in PBMC. The absolute number of coreceptor molecules per cell did not correlate with the viral load. However, the CCR5/CD4 and CXCR4/CD4 ratios in the LN positively correlated with HIV cellular and plasma RNA. Characterization of the viral isolates suggested an association between clinical isolates using a distinct coreceptor and the upregulation of the corresponding chemokine receptor. Conclusions: The ratios of chemokine receptors to CD4 molecules in CD4 T cells from LN is higher than in PBMC and may account for the relative difference in cellular viral load in these compartments. Additionally, the coreceptor/CD4 ratios, particularly in the lymphoid tissue, were highly related to HIV replication.

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