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

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. PBMC and cer...

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Bibliographic Details
Published in:	AIDS (London) Vol. 15; no. 2; pp. 161 - 169
Main Authors:	NOKTA, Mostafa A, LI, Xiao-Dong, NICHOLS, Joan, MALLEN, Michele, POU, Anna, ASMUTH, David, POLLARD, Richard B
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott Williams & Wilkins 26-01-2001
Subjects:	Adult AIDS/HIV Biological and medical sciences CCR5 protein CD4 antigen CD4 Antigens - metabolism CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - virology CXCR4 protein HIV Infections - blood HIV Infections - immunology HIV Infections - virology HIV-1 - genetics HIV-1 - immunology HIV-1 - physiology human immunodeficiency virus Human viral diseases Humans Infectious diseases Leukocytes, Mononuclear - immunology Leukocytes, Mononuclear - virology Lymph Nodes - immunology Lymph Nodes - virology Lymphocyte Activation - immunology Male Medical sciences Middle Aged Receptors, CCR5 - biosynthesis Receptors, CCR5 - metabolism Receptors, CXCR4 - biosynthesis Receptors, CXCR4 - metabolism Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Load Virus Replication Human Immunopathology Prognosis T cell receptor Lymph node Retroviridae AIDS Immune deficiency Lentivirus Density Blood Infection Virus Chemokine Viral disease Risk factor T-Lymphocyte Evolution Replication Human immunodeficiency virus
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Summary:	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. 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. 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 approximately 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. 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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0269-9370 1473-5571
DOI:	10.1097/00002030-200101260-00004