Reduced macrophage infiltration and demyelination in mice lacking the chemokine receptor CCR5 following infection with a neurotropic coronavirus

Virology. 2001 Sep 15;288(1):8-17. doi: 10.1006/viro.2001.1050.


Studies were performed to investigate the contributions of the CC chemokine receptor CCR5 in host defense and disease development following intracranial infection with mouse hepatitis virus (MHV). T cell recruitment was impaired in MHV-infected CCR5(-/-) mice at day 7 postinfection (pi), which correlated with increased (P < or = 0.03) titers within the brain. However, by day 12 pi, T cell infiltration into the CNS of infected CCR5(-/-) and CCR5(+/+) mice was similar and both strains exhibited comparable viral titers, indicating that CCR5 expression is not essential for host defense. Following MHV infection of CCR5(+/+) mice, greater than 50% of cells expressing CCR5 antigen were activated macrophage/microglia (determined by F4/80 antigen expression). In addition, infected CCR5(-/-) mice exhibited reduced (P < or = 0.02) macrophage (CD45(high)F4/80(+)) infiltration, which correlated with a significant reduction (P < or = 0.001) in the severity of demyelination compared to CCR5(+/+) mice. These data indicate that CCR5 contributes to MHV-induced demyelination by allowing macrophages to traffic into the CNS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / pathology
  • Brain / virology*
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / pathology
  • Encephalitis, Viral / immunology*
  • Encephalitis, Viral / pathology
  • Hepatitis, Viral, Animal / immunology
  • Hepatitis, Viral, Animal / pathology
  • Macrophages / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Murine hepatitis virus / isolation & purification
  • Murine hepatitis virus / physiology*
  • Myelin Sheath / pathology
  • Receptors, CCR5 / deficiency
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / physiology*
  • T-Lymphocytes / immunology*
  • Virus Replication*


  • Receptors, CCR5