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 r epresents the high-affinity receptor for HHV-7. In this study, we report th at HHV-7 infection also causes a progressive loss of the surface CXC-chemok ine receptor 4 (CXCR4) in CD4+ T cells, accompanied by a reduced intracellu lar Ca2+ flux and chemotaxis in response to stromal cell-derived factor-1 a lpha (SDF-1 alpha), the specific CXCR4 ligand. Moreover, CXCR4 is downregul ated from the surface of HHV-7-infected T cells independently of CD4. Becau se intracellular CXCR4 antigen and mRMA levels are unaffected in productive ly HHV-7-infected cells, the downregulation of CXCR4 apparently does not in volve a transcritional block. Since CXCR4 functions in association with CD4 to permit entry of several human immunodeficiency virus (HIV) isolates, th e potential of HHV-7 to persistently downregulate the surface expression of CXCR4 may provide never strategies for limiting HIV infection. (C) 1998 by The American Society of Hematology.