title: Viral interactions in human lymphoid tissue: Human herpesvirus 7 suppresses the replication of CCR5-tropic human immunodeficiency virus type 1 via CD4 modulation.
abstract: Human immunodeficiency virus (HIV) infection is often accompanied by infection with other pathogens that affect the clinical course of HIV disease. Here, we identified another virus, human herpesvirus 7 (HHV-7) that interferes with HIV type 1 (HIV-1) replication in human lymphoid tissue, where critical events of HIV disease occur. Like the closely related HHV-6, HHV-7 suppresses the replication of CCR5-tropic (R5) HIV-1 in coinfected blocks of human lymphoid tissue. Unlike HHV-6, which affects HIV-1 by upregulating RANTES, HHV-7 did not upregulate any CCR5-binding chemokine. Rather, the inhibition of R5 HIV-1 by HHV-7 was associated with a marked downregulation of CD4, the cellular receptor shared by HHV-7 and HIV-1. HHV-7-induced CD4 downregulation was sufficient for HIV-1 inhibition, since comparable downregulation of CD4 with cyclotriazadisulfonamide, a synthetic macrocycle that specifically modulates expression of CD4, resulted in the suppression of HIV infection similar to that seen in HHV-7-infected tissues. In contrast to R5 HIV-1, CXCR4-tropic (X4) HIV-1 was only minimally suppressed by HHV-7 coinfection. This selectivity in suppression of R5 and X4 HIV-1 is explained by a suppression of HHV-7 replication in X4- but not in R5-coinfected tissues. These results suggest that HIV-1 and HHV-7 may interfere in lymphoid tissue in vivo, thus potentially affecting the progression of HIV-1 disease. Knowledge of the mechanisms of interaction of HIV-1 with HHV-7, as well as with other pathogens that modulate HIV-1 replication, may provide new insights into HIV pathogenesis and lead to the development of new anti-HIV therapeutic strategies.
authors.affiliation: Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, NIH, Bldg. 10, Rm. 9D58, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lisco
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Grivel
authors.forename: Angélique
authors.initials: A
authors.lastname: Biancotto
authors.forename: Christophe
authors.initials: C
authors.lastname: Vanpouille
authors.forename: Francesco
authors.initials: F
authors.lastname: Origgi
authors.forename: Mauro S
authors.initials: MS
authors.lastname: Malnati
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
authors.forename: Paolo
authors.initials: P
authors.lastname: Lusso
authors.forename: Leonid B
authors.initials: LB
authors.lastname: Margolis
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism*; D015536:Down-Regulation; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D016199:Herpesvirus 7, Human / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008221:Lymphoid Tissue / Q000821:virology*; D014066:Palatine Tonsil / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000821:virology; D014779:Virus Replication
chemical_list: D015704:CD4 Antigens; D019713:Receptors, CCR5