CXC-chemokine receptor 4 is not a coreceptor for human herpesvirus 7 entry into CD4(+) T cells.
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.
Zhang
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Y
Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium. Ying.Zhang@rega.kuleuven.ac.be
Hatse
S
S
De Clercq
E
E
Schols
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D
D000956:Antigens, Viral / Q000276:immunology; D001596:Benzylamines; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D000080027:Cyclams; D016199:Herpesvirus 7, Human / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000956:Antigens, Viral; D001596:Benzylamines; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D011991:Receptors, Virus; C088327:plerixafor