Histopathological Analysis of Adrenal Glands after Simian Varicella Virus Infection

Latent varicella zoster virus (VZV) has been detected in human adrenal glands, raising the possibility of virus-induced adrenal damage and dysfunction during primary infection or reactivation. Rare cases of bilateral adrenal hemorrhage and insufficiency associated with VZV reactivation have been rep...

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Main Authors: Christy S. Niemeyer, Teresa Mescher, Rocio Griggs, David J. Orlicky, Gregory K. Wilkerson, Andrew N. Bubak, James E. Hassell, Brittany Feia, Ravi Mahalingam, Vicki Traina-Dorge, Maria A. Nagel
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/13/7/1245
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author Christy S. Niemeyer
Teresa Mescher
Rocio Griggs
David J. Orlicky
Gregory K. Wilkerson
Andrew N. Bubak
James E. Hassell
Brittany Feia
Ravi Mahalingam
Vicki Traina-Dorge
Maria A. Nagel
author_facet Christy S. Niemeyer
Teresa Mescher
Rocio Griggs
David J. Orlicky
Gregory K. Wilkerson
Andrew N. Bubak
James E. Hassell
Brittany Feia
Ravi Mahalingam
Vicki Traina-Dorge
Maria A. Nagel
author_sort Christy S. Niemeyer
collection DOAJ
description Latent varicella zoster virus (VZV) has been detected in human adrenal glands, raising the possibility of virus-induced adrenal damage and dysfunction during primary infection or reactivation. Rare cases of bilateral adrenal hemorrhage and insufficiency associated with VZV reactivation have been reported. Since there is no animal model for VZV infection of adrenal glands, we obtained adrenal glands from two non-human primates (NHPs) that spontaneously developed varicella from primary simian varicella virus (SVV) infection, the NHP VZV homolog. Histological and immunohistochemical analysis revealed SVV antigen and DNA in the adrenal medulla and cortex of both animals. Adrenal glands were observed to have Cowdry A inclusion bodies, cellular necrosis, multiple areas of hemorrhage, and varying amounts of polymorphonuclear cells. No specific association of SVV antigen with βIII-tubulin-positive nerve fibers was found. Overall, we found that SVV can productively infect NHP adrenal glands, and is associated with inflammation, hemorrhage, and cell death. These findings suggest that further studies are warranted to examine the contribution of VZV infection to human adrenal disease. This study also suggests that VZV infection may present itself as acute adrenal dysfunction with “long-hauler” symptoms of fatigue, weakness, myalgias/arthralgias, and hypotension.
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spelling doaj.art-44083cbac1d84286906a4e499a8d1c0f2023-12-03T13:10:58ZengMDPI AGViruses1999-49152021-06-01137124510.3390/v13071245Histopathological Analysis of Adrenal Glands after Simian Varicella Virus InfectionChristy S. Niemeyer0Teresa Mescher1Rocio Griggs2David J. Orlicky3Gregory K. Wilkerson4Andrew N. Bubak5James E. Hassell6Brittany Feia7Ravi Mahalingam8Vicki Traina-Dorge9Maria A. Nagel10Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Pathology, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Comparative Medicine, Keeling Center for Comparative Medicine and Research, University of Texas, MD Anderson Cancer Center, Bastrop, TX 78602, USADepartment of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USAMicrobiology Division, Tulane National Primate Research Center, Tulane University, Covington, LA 70433, USADepartment of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USALatent varicella zoster virus (VZV) has been detected in human adrenal glands, raising the possibility of virus-induced adrenal damage and dysfunction during primary infection or reactivation. Rare cases of bilateral adrenal hemorrhage and insufficiency associated with VZV reactivation have been reported. Since there is no animal model for VZV infection of adrenal glands, we obtained adrenal glands from two non-human primates (NHPs) that spontaneously developed varicella from primary simian varicella virus (SVV) infection, the NHP VZV homolog. Histological and immunohistochemical analysis revealed SVV antigen and DNA in the adrenal medulla and cortex of both animals. Adrenal glands were observed to have Cowdry A inclusion bodies, cellular necrosis, multiple areas of hemorrhage, and varying amounts of polymorphonuclear cells. No specific association of SVV antigen with βIII-tubulin-positive nerve fibers was found. Overall, we found that SVV can productively infect NHP adrenal glands, and is associated with inflammation, hemorrhage, and cell death. These findings suggest that further studies are warranted to examine the contribution of VZV infection to human adrenal disease. This study also suggests that VZV infection may present itself as acute adrenal dysfunction with “long-hauler” symptoms of fatigue, weakness, myalgias/arthralgias, and hypotension.https://www.mdpi.com/1999-4915/13/7/1245varicella zoster virussimian varicella virusadrenal glandsadrenal dysfunctionhypothalamic-pituitary-adrenal axis
spellingShingle Christy S. Niemeyer
Teresa Mescher
Rocio Griggs
David J. Orlicky
Gregory K. Wilkerson
Andrew N. Bubak
James E. Hassell
Brittany Feia
Ravi Mahalingam
Vicki Traina-Dorge
Maria A. Nagel
Histopathological Analysis of Adrenal Glands after Simian Varicella Virus Infection
Viruses
varicella zoster virus
simian varicella virus
adrenal glands
adrenal dysfunction
hypothalamic-pituitary-adrenal axis
title Histopathological Analysis of Adrenal Glands after Simian Varicella Virus Infection
title_full Histopathological Analysis of Adrenal Glands after Simian Varicella Virus Infection
title_fullStr Histopathological Analysis of Adrenal Glands after Simian Varicella Virus Infection
title_full_unstemmed Histopathological Analysis of Adrenal Glands after Simian Varicella Virus Infection
title_short Histopathological Analysis of Adrenal Glands after Simian Varicella Virus Infection
title_sort histopathological analysis of adrenal glands after simian varicella virus infection
topic varicella zoster virus
simian varicella virus
adrenal glands
adrenal dysfunction
hypothalamic-pituitary-adrenal axis
url https://www.mdpi.com/1999-4915/13/7/1245
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