title: CD134 is a cellular receptor specific for human herpesvirus-6B entry.
abstract: Human herpesvirus-6B (HHV-6B) is a T lymphotropic β-herpesvirus that is clearly distinct from human herpesvirus-6A (HHV-6A) according to molecular biological features. The International Committee on Taxonomy of Viruses recently classified HHV-6B as a separate species. The primary HHV-6B infection causes exanthem subitum and is sometimes associated with severe encephalopathy. More than 90% of the general population is infected with HHV-6B during childhood, and the virus remains throughout life as a latent infection. HHV-6B reactivation causes encephalitis in immunosuppressed patients. The cellular receptor for HHV-6A entry was identified as human CD46, but the receptor for HHV-6B has not been clear. Here we found that CD134, a member of the TNF receptor superfamily, functions as a specific entry receptor for HHV-6B. A T-cell line that is normally nonpermissive for HHV-6B infection became highly susceptible to infection when CD134 was overexpressed. CD134 was down-regulated in HHV-6B-infected T cells. Soluble CD134 interacted with the HHV-6B glycoprotein complex that serves as a viral ligand for cellular receptor, which inhibited HHV-6B but not HHV-6A infection in target cells. The identification of CD134 as an HHV-6B specific entry receptor provides important insight into understanding HHV-6B entry and its pathogenesis.
authors.affiliation: Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Huamin
authors.initials: H
authors.lastname: Tang
authors.forename: Satoshi
authors.initials: S
authors.lastname: Serada
authors.forename: Akiko
authors.initials: A
authors.lastname: Kawabata
authors.forename: Megumi
authors.initials: M
authors.lastname: Ota
authors.forename: Emi
authors.initials: E
authors.lastname: Hayashi
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamanishi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Mori
mesh_terms: D005434:Flow Cytometry; D057809:HEK293 Cells; D015654:Herpesvirus 6, Human / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D010957:Plasmids / Q000235:genetics; D053262:Receptors, OX40 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D014760:Viral Fusion Proteins / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D053262:Receptors, OX40; C505716:TNFRSF4 protein, human; D014760:Viral Fusion Proteins
keywords: gQ1; gQ2; viral entry