title: Detection of severe acute respiratory syndrome coronavirus in the brain: potential role of the chemokine mig in pathogenesis.
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- gamma (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- gamma -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.
authors.affiliation: Guangzhou Institute of Respiratory Diseases, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Shuqing
authors.initials: S
authors.lastname: Zhong
authors.forename: Jinghua
authors.initials: J
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Xinwei
authors.initials: X
authors.lastname: Wu
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Deng
authors.forename: Jingqiang
authors.initials: J
authors.lastname: Zhang
authors.forename: Nanshan
authors.initials: N
authors.lastname: Zhong
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Ding
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology / Q000821:virology*; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000378:metabolism*; D017809:Fatal Outcome; D006801:Humans; D008297:Male; D045473:Severe acute respiratory syndrome-related coronavirus / Q000302:isolation & purification*; D045169:Severe Acute Respiratory Syndrome / Q000378:metabolism* / Q000473:pathology / Q000821:virology
chemical_list: C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D019743:Chemokines, CXC