CD134 is a cellular receptor specific for human herpesvirus-6B entry

Proc Natl Acad Sci U S A. 2013 May 28;110(22):9096-9. doi: 10.1073/pnas.1305187110. Epub 2013 May 14.


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.

Keywords: gQ1; gQ2; viral entry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Flow Cytometry
  • HEK293 Cells
  • Herpesvirus 6, Human / metabolism
  • Herpesvirus 6, Human / physiology*
  • Humans
  • Plasmids / genetics
  • Receptors, OX40 / metabolism*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology
  • Viral Fusion Proteins / metabolism*
  • Virus Internalization*


  • Receptors, OX40
  • TNFRSF4 protein, human
  • Viral Fusion Proteins