Progressive and persistent downregulation of surface CXCR4 in CD4(+) T cells infected with human herpesvirus 7.
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.
Secchiero
P
P
Institute of Human Virology, University of Maryland, Baltimore, MD; and the Human Anatomy Section, Department of Morphology and Embriology, University of Ferrara, Ferrara, Italy. secchier@umbi.umd.edu
Zella
D
D
Barabitskaja
O
O
Reitz
M S
MS
Capitani
S
S
Gallo
R C
RC
Zauli
G
G
D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology / Q000821:virology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D015536:Down-Regulation / Q000276:immunology*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000472:pathogenicity; D006566:Herpesviridae Infections / Q000276:immunology*; D016199:Herpesvirus 7, Human / Q000472:pathogenicity*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*
D015704:CD4 Antigens; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D002118:Calcium