CXC-chemokine receptor 4 is not a coreceptor for human herpesvirus 7 entry into CD4(+) T cells.

Abstract

Human herpesvirus 7 (HHV-7) is a T-lymphotropic virus which utilizes the CD4 receptor as its main receptor to enter the target cells. Hence, HHV-7 can interfere with human immunodeficiency virus type 1 (HIV-1) infection in CD4(+) T cells. It was recently suggested that the CXC chemokine receptor 4 (CXCR4), which was found to be a crucial coreceptor for T-tropic HIV-1 strains, may also play a role in the HHV-7 infection process. However, the results presented here demonstrate that CXCR4 is not involved in HHV-7 infection. The natural ligand of CXCR4, SDF-1alpha, was not able to inhibit HHV-7 infection in SupT1 cells or in CD8(+) T-cell-depleted peripheral blood mononuclear cells. Also, AMD3100, a specific CXCR4 antagonist with potent antiviral activity against T-tropic HIV strains (50% inhibitory concentration ¿IC(50), 1 to 10 ng/ml), completely failed to inhibit HHV-7 infection (IC(50), >250 microg/ml). Thus, two different agents known to specifically interact with CXCR4 were not able to inhibit HHV-7 infection. Other T-lymphoid cell lines, expressing both CD4 and CXCR4 (e.g., HUT-78 and MT-4) could not be infected by HHV-7. In addition, the CD4-transfected cell lines HOS. CD4 and U87.CD4 and the CD4/CXCR4 double-transfected cell lines HOS. CD4.CXCR4 and U87.CD4.CXCR4 were not infectable with HHV-7. Also, we found no down-regulation of surface-bound or intracellular CXCR4 in HHV-7-infected CD4(+) T cells. As compared to uninfected SupT1 cells, stromal cell-derived factor 1alpha (SDF-1alpha)/CXCR4-mediated intracellular calcium flux was unchanged in SupT1 cells that were acutely or persistently infected with HHV-7. All these data argue against CXCR4 as a receptor involved in the HHV-7 infection process.

• Authors: Y Zhang, S Hatse, E De Clercq, D Schols
• Journal: Journal of virology (J Virol) Vol. 74 Issue 4 Pg. 2011-6 (Feb 2000) ISSN: 0022-538X [Print] United States
• PMID: 10644374 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Viral
• Benzylamines
• CXCL12 protein, human
• Chemokine CXCL12
• Chemokines, CXC
• Cyclams
• Heterocyclic Compounds
• Receptors, CXCR4
• Receptors, Virus
• plerixafor

Topics

• Antigens, Viral (immunology)
• Benzylamines
• CD4-Positive T-Lymphocytes (drug effects, virology)
• CD8-Positive T-Lymphocytes (metabolism, virology)
• Chemokine CXCL12
• Chemokines, CXC (pharmacology)
• Cyclams
• Herpesvirus 7, Human (immunology, metabolism, physiology)
• Heterocyclic Compounds (pharmacology)
• Humans
• Receptors, CXCR4 (antagonists & inhibitors, metabolism)
• Receptors, Virus (metabolism)
• Tumor Cells, Cultured