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VZV Infection of Primary Human Adrenal Cortical Cells Produces a Proinflammatory Environment without Cell Death

Virus infection of adrenal glands can disrupt secretion of mineralocorticoids, glucocorticoids, and sex hormones from the cortex and catecholamines from the medulla, leading to a constellation of symptoms such as fatigue, dizziness, weight loss, nausea, and muscle and joint pain. Specifically, varic...

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Autores principales: Niemeyer, Christy S., Mescher, Teresa, Bubak, Andrew N., Medina, Eva M., Hassell, James E., Nagel, Maria A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030771/
https://www.ncbi.nlm.nih.gov/pubmed/35458404
http://dx.doi.org/10.3390/v14040674
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author Niemeyer, Christy S.
Mescher, Teresa
Bubak, Andrew N.
Medina, Eva M.
Hassell, James E.
Nagel, Maria A.
author_facet Niemeyer, Christy S.
Mescher, Teresa
Bubak, Andrew N.
Medina, Eva M.
Hassell, James E.
Nagel, Maria A.
author_sort Niemeyer, Christy S.
collection PubMed
description Virus infection of adrenal glands can disrupt secretion of mineralocorticoids, glucocorticoids, and sex hormones from the cortex and catecholamines from the medulla, leading to a constellation of symptoms such as fatigue, dizziness, weight loss, nausea, and muscle and joint pain. Specifically, varicella zoster virus (VZV) can produce bilateral adrenal hemorrhage and adrenal insufficiency during primary infection or following reactivation. However, the mechanisms by which VZV affects the adrenal glands are not well-characterized. Herein, we determined if primary human adrenal cortical cells (HAdCCs) infected with VZV support viral replication and produce a proinflammatory environment. Quantitative PCR showed VZV DNA increasing over time in HAdCCs, yet no cell death was seen at 3 days post-infection by TUNEL staining or Western Blot analysis with PARP and caspase 9 antibodies. Compared to conditioned supernatant from mock-infected cells, supernatant from VZV-infected cells contained significantly elevated IL-6, IL-8, IL-12p70, IL-13, IL-4, and TNF-α. Overall, VZV can productively infect adrenal cortical cells in the absence of cell death, suggesting that these cells may be a potential reservoir for ongoing viral replication and proinflammatory cytokine production, leading to chronic adrenalitis and dysfunction.
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spelling pubmed-90307712022-04-23 VZV Infection of Primary Human Adrenal Cortical Cells Produces a Proinflammatory Environment without Cell Death Niemeyer, Christy S. Mescher, Teresa Bubak, Andrew N. Medina, Eva M. Hassell, James E. Nagel, Maria A. Viruses Article Virus infection of adrenal glands can disrupt secretion of mineralocorticoids, glucocorticoids, and sex hormones from the cortex and catecholamines from the medulla, leading to a constellation of symptoms such as fatigue, dizziness, weight loss, nausea, and muscle and joint pain. Specifically, varicella zoster virus (VZV) can produce bilateral adrenal hemorrhage and adrenal insufficiency during primary infection or following reactivation. However, the mechanisms by which VZV affects the adrenal glands are not well-characterized. Herein, we determined if primary human adrenal cortical cells (HAdCCs) infected with VZV support viral replication and produce a proinflammatory environment. Quantitative PCR showed VZV DNA increasing over time in HAdCCs, yet no cell death was seen at 3 days post-infection by TUNEL staining or Western Blot analysis with PARP and caspase 9 antibodies. Compared to conditioned supernatant from mock-infected cells, supernatant from VZV-infected cells contained significantly elevated IL-6, IL-8, IL-12p70, IL-13, IL-4, and TNF-α. Overall, VZV can productively infect adrenal cortical cells in the absence of cell death, suggesting that these cells may be a potential reservoir for ongoing viral replication and proinflammatory cytokine production, leading to chronic adrenalitis and dysfunction. MDPI 2022-03-25 /pmc/articles/PMC9030771/ /pubmed/35458404 http://dx.doi.org/10.3390/v14040674 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Niemeyer, Christy S.
Mescher, Teresa
Bubak, Andrew N.
Medina, Eva M.
Hassell, James E.
Nagel, Maria A.
VZV Infection of Primary Human Adrenal Cortical Cells Produces a Proinflammatory Environment without Cell Death
title VZV Infection of Primary Human Adrenal Cortical Cells Produces a Proinflammatory Environment without Cell Death
title_full VZV Infection of Primary Human Adrenal Cortical Cells Produces a Proinflammatory Environment without Cell Death
title_fullStr VZV Infection of Primary Human Adrenal Cortical Cells Produces a Proinflammatory Environment without Cell Death
title_full_unstemmed VZV Infection of Primary Human Adrenal Cortical Cells Produces a Proinflammatory Environment without Cell Death
title_short VZV Infection of Primary Human Adrenal Cortical Cells Produces a Proinflammatory Environment without Cell Death
title_sort vzv infection of primary human adrenal cortical cells produces a proinflammatory environment without cell death
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030771/
https://www.ncbi.nlm.nih.gov/pubmed/35458404
http://dx.doi.org/10.3390/v14040674
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