Progressive and persistent downregulation of surface CXCR4 in CD4(+) T cells infected with human herpesvirus 7.

Abstract

We have previously shown that infection of CD4(+) T lymphocytes with the T-lymphotropic human herpesvirus 7 (HHV-7) downregulates surface CD4, which represents the high-affinity receptor for HHV-7. In this study, we report that HHV-7 infection also causes a progressive loss of the surface CXC-chemokine receptor 4 (CXCR4) in CD4(+) T cells, accompanied by a reduced intracellular Ca2+ flux and chemotaxis in response to stromal cell-derived factor-1 (SDF-1), the specific CXCR4 ligand. Moreover, CXCR4 is downregulated from the surface of HHV-7-infected T cells independently of CD4. Because intracellular CXCR4 antigen and mRNA levels are unaffected in productively HHV-7-infected cells, the downregulation of CXCR4 apparently does not involve a transcritional block. Since CXCR4 functions in association with CD4 to permit entry of several human immunodeficiency virus (HIV) isolates, the potential of HHV-7 to persistently downregulate the surface expression of CXCR4 may provide novel strategies for limiting HIV infection.

• Authors: P Secchiero, D Zella, O Barabitskaja, M S Reitz, S Capitani, R C Gallo, G Zauli
• Journal: Blood (Blood) Vol. 92 Issue 12 Pg. 4521-8 (Dec 15 1998) ISSN: 0006-4971 [Print] United States
• PMID: 9845516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD4 Antigens
• CXCL12 protein, human
• Chemokine CXCL12
• Chemokines, CXC
• RNA, Messenger
• Receptors, CXCR4
• Calcium

Topics

• CD4 Antigens (metabolism)
• CD4-Positive T-Lymphocytes (drug effects, metabolism, physiology, virology)
• Calcium (metabolism)
• Cell Line
• Cells, Cultured
• Chemokine CXCL12
• Chemokines, CXC (pharmacology)
• Chemotaxis (drug effects)
• Down-Regulation (immunology)
• Flow Cytometry
• Fluorescent Antibody Technique, Indirect
• HIV Infections (immunology)
• HIV-1 (pathogenicity)
• Herpesviridae Infections (immunology)
• Herpesvirus 7, Human (pathogenicity)
• Humans
• Intracellular Fluid (metabolism)
• RNA, Messenger (analysis)
• Receptors, CXCR4 (genetics, metabolism)