Get access

CD46 on glial cells can function as a receptor for viral glycoprotein-mediated cell–cell fusion

Authors

  • Riccardo Cassiani-Ingoni,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
    2. Department of Human Physiology and Pharmacology, Center of Excellence in Biology and Molecular Medicine, University of Rome La Sapienza, Rome, Italy
    Search for more papers by this author
  • Heather L. Greenstone,

    1. Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Donatella Donati,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Anna Fogdell-Hahn,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Elena Martinelli,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Daniel Refai,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Roland Martin,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Edward A. Berger,

    1. Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Steven Jacobson

    Corresponding author
    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
    • Bldg. 10, Rm. 5B16, National Institutes of Health, Bethesda, MD 20892
    Search for more papers by this author

  • This article is a US Government work and, as such, is in the public domain in the United States of America.

Abstract

Membrane cofactor protein (CD46) is a regulator of complement activation that also serves as the entry receptor for human herpes virus 6 (HHV-6) and measles virus (MV) into human cells. While it is clear that oligodendrocytes and astrocytes are cell types commonly infected by these viruses, it is unclear whether oligodendrocytes express CD46, or which are the cellular mechanisms underlying the infection. We show that adult oligodendrocytes, as well as astrocytes and microglial cells, express CD46 on the cellular surface. Moreover, we employed a quantitative fusion assay to demonstrate that HHV-6A infection of T lymphocytes enables cell–cell fusion of these cells to astrocytes or to oligodendroglial cells. This fusion is mediated by the interaction between viral glycoproteins expressed on the membrane of the infected cells and CD46 on the glial targets, and is also observed using cells expressing recombinant MV glycoproteins. These data suggest a mechanism that involves cell–cell fusion by which certain viruses could spread the infection from the periphery to the cells in the nervous system. Published 2005 Wiley-Liss, Inc.

Get access to the full text of this article

Ancillary