CD4 is a critical component of the receptor for human herpesvirus 7: interference with human immunodeficiency virus.

Abstract

In this study, we demonstrate that the glycoprotein CD4, a member of the immunoglobulin superfamily, is a critical component of the receptor for human herpesvirus 7 (IIHV-7), a recently discovered T-lymphotropic human herpesvirus. A selective and progressive downregulation of the surface membrane expression of CD4 was observed in human CD4+ T cells in the course of HHV-7 infection. Various murine monoclonal antibodies to CD4 and the recombinant soluble form of human CD4 caused a dose-dependent inhibition of HHV-7 infection in primary CD4+ T lymphocytes. Moreover, radiolabeled HHIV-7 specifically bound to cervical carcinoma cells (HeLa) expressing human CD4. A marked reciprocal interference was observed between HHV-7 and human immunodericiency virus (HIV), the retrovirus that causes the acquired immunodeficiency syndrome and also uses CD4 as a receptor. Previous exposure of CD4+ T cells to HHV-7 dramatically interfered with infection by both primary and in vitro-passaged HIV-1 isolates. Reciprocally, persistent infection with IIV-1 or treatment with the soluble form of gpl20, the CD4-binding envelope glycoprotein of HIV-1, rendered CD4+ T cells resistant to HHV-7 infection. These data indicate that CD4 is critically involved in the receptor mechanism for HHV-7. The antagonistic effect between HHV-7 and HIV could be exploited to devise therapeutic approaches to AIDS.

CD68+cells of monocyte/macrophage lineage in the environment of AIDS-associated and classic-sporadic Kaposi sarcoma are singly or doubly infected with human herpesviruses 7 and 6B

“…3 and 27, see ref. 29) and indeed the CD4 molecule appears to be a component of the viral receptor (30,31). Attempts to infect terminally differentiated macrophages have not been successful (32).…”

Latent infection of human herpesvirus 7 in CD4+ T lymphocytes

“…HHV-7 is a T-lymphotropic virus, using CD4 as a cellular receptor [Yasukawa et al, 1997], that replicate in CD4 þ T cells and the SupT1 cell line in vitro [Lusso et al, 1994]. Kempf et al [1997] reported that HHV-7 antigens were detected in CD68þ monocyte/macrophage lineage cells in tissues from patients with Kaposi's sarcoma.…”

CD4 down-modulation by ganglioside and phorbol ester inhibits human herpesvirus 7 infection

“…The present work and the recent study by Lusso et al (1994) have shown that HHV-7 and HIV-1 compete for cell surface CD4 as their binding receptor. Identification of the HHV-7 structure that binds to the CD4 molecule might allow the development of a subcomponent peptide derived from HHV-7 that selectively inhibits HIV binding but does not affect CD4 + T cell functions.…”

“…Lusso et al (1994) and our group (Furukawa et al, 1994) have recently found that HHV-7 infection results in a marked decline in surface CD4 expression and functional alteration of CD4 + T cells. It is well known that such down-modulation of expression of surface CD4, which is the receptor for human immunodeficiency virus-1 (HIV-1), also occurs in HIV-l-infected cells (Hoxie et al, 1986a;Stevenson et al, 1987;Salmon et al, 1988;Kawamura et al, 1989;Geleziunas et aI., 1994).…”

“…Therefore, it can be anticipated that the binding of HHV-7 to the CD4 molecule is one of the causes of the down-modulation of surface CD4 expression in HHV-7-infected cells. Lusso et al (1994) have recently reported that anti-CD4 MAbs and the soluble form of CD4 inhibit HHV-7 infection. Moreover, they showed that exposure of CD4 + T cells to HHV-7 interfered with infection by HIV-1 and that persistent infection with HIV-1 or treatment with the soluble form of HIV-1 glycoprotein gpl20 rendered CD4 + T cells resistant to HHV-7 infection.…”