title: Varicella zoster virus vasculopathy: analysis of virus-infected arteries.
abstract: OBJECTIVE
  Varicella zoster virus (VZV) is an under-recognized yet treatable cause of stroke. No animal model exists for stroke caused by VZV infection of cerebral arteries. Thus, we analyzed cerebral and temporal arteries from 3 patients with VZV vasculopathy to identify features that will help in diagnosis and lead to a better understanding of VZV-induced vascular remodeling.
  
  
  METHODS
  Normal and VZV-infected cerebral and temporal arteries were examined histologically and by immunohistochemistry using antibodies directed against VZV, endothelium, and smooth muscle actin and myosin.
  
  
  RESULTS
  All VZV-infected arteries contained 1) a disrupted internal elastic lamina; 2) a hyperplastic intima composed of cells expressing α-smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain (SM-myosin) but not endothelial cells expressing CD31; and 3) decreased medial smooth muscle cells. The location of VZV antigen, degree of neointimal thickening, and disruption of the media were related to the duration of disease.
  
  
  CONCLUSIONS
  The presence of VZV primarily in the adventitia early in infection and in the media and intima later supports the notion that after reactivation from ganglia, VZV spreads transaxonally to the arterial adventitia followed by transmural spread of virus. Disruption of the internal elastic lamina, progressive intimal thickening with cells expressing α-SMA and SM-MHC, and decreased smooth muscle cells in the media are characteristic features of VZV vasculopathy. Stroke in VZV vasculopathy may result from changes in arterial caliber and contractility produced in part by abnormal accumulation of smooth muscle cells and myofibroblasts in thickened neointima and disruption of the media.
authors.affiliation: Department of Neurology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Box B182, Aurora, CO 80045, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Nagel
authors.forename: I
authors.initials: I
authors.lastname: Traktinskiy
authors.forename: Y
authors.initials: Y
authors.lastname: Azarkh
authors.forename: B
authors.initials: B
authors.lastname: Kleinschmidt-DeMasters
authors.forename: T
authors.initials: T
authors.lastname: Hedley-Whyte
authors.forename: A
authors.initials: A
authors.lastname: Russman
authors.forename: E M
authors.initials: EM
authors.lastname: VanEgmond
authors.forename: K
authors.initials: K
authors.lastname: Stenmark
authors.forename: M
authors.initials: M
authors.lastname: Frid
authors.forename: R
authors.initials: R
authors.lastname: Mahalingam
authors.forename: M
authors.initials: M
authors.lastname: Wellish
authors.forename: A
authors.initials: A
authors.lastname: Choe
authors.forename: R
authors.initials: R
authors.lastname: Cordery-Cotter
authors.forename: R J
authors.initials: RJ
authors.lastname: Cohrs
authors.forename: D
authors.initials: D
authors.lastname: Gilden
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D020521:Stroke / Q000473:pathology* / Q000821:virology; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*; D014777:Virus Diseases / Q000378:metabolism / Q000473:pathology*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018995:Myosin Heavy Chains