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

• 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
• DOI: 10.1097/00002030-200101260-00004
• EISSN: 1473-5571
• ISSN: 0269-9370

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.