Role of beta-chemokines in HIV-1 infection of dendritic cells maturing from CD34+ stem cells.

Abstract

OBJECTIVES:

To study the susceptibility to infection by different strains of HIV-1 viruses and the roles of chemokines (macrophage inflammatory protein-1alpha [MIP-1alpha], MIP-1beta, and regulated-on-activation-T-expressed-and-secreted [RANTES]) in CD34+ stem cells maturing into dendritic cells (DC).

DESIGN:

It has been controversial whether CD34+ stem cells are susceptible to HIV-1 infection and whether high levels of beta-chemokines are beneficial for suppressing HIV-1 infection during DC maturation. These questions were addressed using different strains of HIV-1 and CD34+ stem cells taken from cord blood and cultured with granulocyte-macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) to generate mature DC.

METHODS:

CD34+ stem cells were exposed with M-tropic virus Ba-L or T-tropic viruses IIIB or Rut at day 1. Beta-chemokines were added to some cells before the virus and kept throughout the culture. Virus replication was measured throughout the maturation of these cells into CD1a+ DC and CD1a- CD14+ cells using enzyme-linked immunosorbent assay (ELISA) for p24, nested polymerase chain reaction (PCR) for env and intracellular p24 detection by flow cytometry.

RESULTS:

First, CD34+ stem cells acquired or were infected by live virus because maturing cells showed infection by both M- and T-tropic viruses. Second, the viruses replicated actively during the maturation of CD34+ stem cells toward CD1a+ DC and CD1a- CD14+ cells. Third, beta-chemokines suppressed infection by M-tropic virus Ba-L. And finally, beta-chemokines enhanced infection by T-tropic viruses IIIB and Rut.

CONCLUSIONS:

In addition to the initial anti-M-tropic virus effect by beta-chemokines, selective pressure on viruses may also result because of an increase in susceptibility to T-tropic virus. Caution should be taken when evaluating the effect of beta-chemokine receptor agonists in AIDS therapy.

• Authors: H Wang, N J English, C D Reid, J E Merson, S C Knight
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 21 Issue 3 Pg. 179-88 (Jul 01 1999) ISSN: 1525-4135 [Print] United States
• PMID: 10421240 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD34
• Chemokine CCL3
• Chemokine CCL4
• Chemokines, CC
• Macrophage Inflammatory Proteins
• Receptors, CCR5
• Receptors, CXCR4

Topics

• Antigens, CD34
• Cell Count
• Chemokine CCL3
• Chemokine CCL4
• Chemokines, CC (physiology)
• Dendritic Cells (virology)
• Gene Expression
• HIV-1 (pathogenicity)
• Hematopoietic Stem Cells (virology)
• Humans
• Macrophage Inflammatory Proteins (physiology)
• Macrophages (virology)
• Receptors, CCR5 (genetics)
• Receptors, CXCR4 (genetics)
• T-Lymphocytes (virology)