Detection of Severe Acute Respiratory Syndrome Coronavirus in the Brain: Potential Role of the Chemokine Mig in Pathogenesis
Top Cited Papers
Open Access
- 15 October 2005
- journal article
- case report
- Published by Oxford University Press (OUP) in Clinical Infectious Diseases
- Vol. 41 (8), 1089-1096
- https://doi.org/10.1086/444461
Abstract
Background. Previous studies have shown that common human coronavirus might be neurotropic, although it was first isolated as a pathogen of the respiratory tract. We noticed that a few patients with severe acute respiratory syndrome (SARS) experienced central nervous symptoms during the course of illness. In the present study, we isolated a SARS coronavirus strain from a brain tissue specimen obtained from a patient with SARS with significant central nervous symptoms. Methods. Using transmission electronic microscopy and nested reverse transcription–polymerase chain reaction, the causative pathogen was identified in cultures of a brain tissue specimen obtained from the patient with SARS. Histopathologic examination of the brain tissue was performed using the methods of immunohistochemistry analysis and double immunofluorescence staining. Fifteen cytokines and chemokines were detected in the blood of the patient with SARS by means of a bead-based multiassay system. Results. A fragment specific for SARS human coronavirus was amplified from cultures of the brain suspension, and transmission electronic microscopy revealed the presence of an enveloped virus morphologically compatible with a coronavirus isolated in the cultures. Pathologic examination of the brain tissue revealed necrosis of neuron cells and broad hyperplasia of gliocytes. Immunostaining demonstrated that monokine induced by interferon-Γ (Mig) was expressed in gliocytes with the infiltration of CD68+ monocytes/macrophages and CD3+ T lymphocytes in the brain mesenchyme. Cytokine/chemokine assay revealed that levels of interferon-Γ–inducible protein 10 and Mig in the blood were highly elevated, although the levels of other cytokines and chemokines were close to normal. Conclusions. This study provides direct evidence that SARS human coronavirus is capable of infecting the central nervous system, and that Mig might be involved in the brain immunopathology of SARS.This publication has 30 references indexed in Scilit:
- Plasma inflammatory cytokines and chemokines in severe acute respiratory syndromeClinical and Experimental Immunology, 2004
- Expression of Lymphocytes and Lymphocyte Subsets in Patients with Severe Acute Respiratory SyndromeClinical Infectious Diseases, 2003
- SARS: understanding the coronavirus: Apoptosis may explain lymphopenia of SARSBMJ, 2003
- Are clinical negligence and legal action related?BMJ, 2003
- Multiplex analysis of cytokines in the blood of cynomolgus macaques naturally infected with Ebola virus (reston serotype)**Journal of Medical Virology, 2001
- Patterns of oligodendrocyte pathology in coronavirus-induced subacute demyelinating encephalomyelitis in the lewis ratGlia, 1997
- Structural and functional analysis of the S proteins of two human coronavirus OC43 strains adapted to growth in different cellsArchiv für die gesamte Virusforschung, 1996
- Viremic dissemination of mouse hepatitis virus-JHM following intranasal inoculation of miceArchiv für die gesamte Virusforschung, 1992
- Effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain.The Journal of Experimental Medicine, 1990
- Adoptive transfer of EAE-like lesions from rats with coronavirus-induced demyelinating encephalomyelitisNature, 1983