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

Abstract

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.

• Authors: W G Glass, M T Liu, W A Kuziel, T E Lane
• Journal: Virology (Virology) Vol. 288 Issue 1 Pg. 8-17 (Sep 15 2001) ISSN: 0042-6822 [Print] United States
• PMID: 11543653 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2001 Academic Press.

Chemical References

• Receptors, CCR5

Topics

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