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.
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Information & Authors
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Copyright © 2011 by AAN Enterprises, Inc.
Publication History
Received: February 18, 2011
Accepted: April 6, 2011
Published online: July 13, 2011
Published in print: July 26, 2011
Disclosure
Dr. Nagel receives research support from the NIH. I. Traktinskiy reports no disclosures. Dr. Azarkh receives research support from the NIH. Dr. Kleinschmidt-DeMasters reports no disclosures. Dr. Hedley-Whyte serves on the editorial board of Human Pathology and holds stock/stock options in Becton Dickinson. Dr. Russman serves on speakers' bureaus for Boehringer Ingelheim and Pfizer Inc and receives research support from the NIH. Dr. VanEgmond reports no disclosures. Dr. Stenmark serves on the editorial boards of the American Journal of Respiratory and Critical Care Medicine, the American Journal of Respiratory Cell and Molecular Biology, the American Journal of Physiology–Lung Cellular and Molecular Physiology, and as an Associate Editor for Pulmonary Circulation; and receives research support from the NIH. Dr. Frid reports no disclosures. Dr. Mahalingam serves on the editorial board of the Journal of Neurovirology and receives research support from the NIH. M. Wellish and A. Choe report no disclosures. Dr. Cordery-Cotter reports no disclosures. Dr. Cohrs serves on the editorial board of Archives of Clinical Microbiology and receives research support from the NIH. Dr. Gilden has received a speaker honorarium from Merck & Co., Inc.; serves as Senior Associate Editor for the Journal of Neurovirology and on the editorial boards of In Vivo, the Journal of Virology, Scientific American Medicine, Virus Genes, and Neurology®; has served as a consultant for Teva Pharmaceutical Industries Ltd. and Epiphany Laboratories; and receives research support from the NIH.
Authors
Author Contributions
Dr. Nagel: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, contribution of vital reagents/tools/patients, acquisition of data, study supervision. I. Traktinskiy: study concept or design, analysis or interpretation of data, contribution of vital reagents/tools/patients, acquisition of data, study supervision. Dr. Azarkh: analysis or interpretation of data. Dr. Kleinschmidt-DeMasters: drafting/revising the manuscript, analysis or interpretation of data. Dr. Hedley-Whyte: drafting/revising the manuscript, contribution of vital reagents/tools/patients. Dr. Russman: drafting/revising the manuscript, analysis or interpretation of data, acquisition of data. Dr. VanEgmond: analysis or interpretation of data. Dr. Stenmark: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, obtaining funding. Dr. Frid: drafting/revising the manuscript, study concept or design, contribution of vital reagents/tools/patients, study supervision. Dr. Mahalingam: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, contribution of vital reagents/tools/patients, acquisition of data. M. Wellish: study concept or design. A. Choe: study concept or design, analysis or interpretation of data, acquisition of data, statistical analysis. Dr. Cordery-Cotter: analysis or interpretation of data, contribution of vital reagents/tools/patients, study supervision. Dr. Cohrs: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, contribution of vital reagents/tools/patients, acquisition of data, obtaining funding. Dr. Gilden: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, contribution of vital reagents/tools/patients, acquisition of data, study supervision, obtaining funding.
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