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Insights into the role of immunosenescence during varicella zoster virus infection (shingles) in the aging cell model
Varicella zoster virus (VZV) is the etiological agent of shingles, a painful skin rash that affects a significant proportion of the elderly population. In the present study, we used two aging cell models, Hutchinson-Gilford progeria syndrome (HGPS) fibroblasts and stress or replicative senescence-in...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742108/ https://www.ncbi.nlm.nih.gov/pubmed/26473290 |
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author | Kim, Ji-Ae Park, Seul-Ki Kumar, Mukesh Lee, Chan-Hee Shin, Ok Sarah |
author_facet | Kim, Ji-Ae Park, Seul-Ki Kumar, Mukesh Lee, Chan-Hee Shin, Ok Sarah |
author_sort | Kim, Ji-Ae |
collection | PubMed |
description | Varicella zoster virus (VZV) is the etiological agent of shingles, a painful skin rash that affects a significant proportion of the elderly population. In the present study, we used two aging cell models, Hutchinson-Gilford progeria syndrome (HGPS) fibroblasts and stress or replicative senescence-induced normal human dermal fibroblasts (NHDFs), to investigate age-associated susceptibility to VZV infection. VZV infectivity titers were significantly associated with donor age in HGPS fibroblasts and senescence induction in NHDFs. High throughput RNA-sequencing (RNA-seq) analysis was performed to assess global and dynamic changes in the host transcriptomes of VZV-infected aging cells. Analysis of differentially expressed genes (DEGs) indicated that VZV infection in aged HGPS fibroblasts resembled that in senescent NHDFs, particularly in terms of genes associated with pattern recognition receptors in virus sensing network, providing novel insights into the mechanisms of senescence-associated susceptibility to VZV infection. Additionally, we identified stimulator of interferon genes (STING) as a potential VZV sensing receptor. Knockdown of STING expression resulted in increased viral replication in primary fibroblasts, whereas STING overexpression led to suppression of VZV plaque formation. In conclusion, our findings highlight the important role of immunosenescence following VZV infection and provide significant insights into the mechanisms underlying cellular sensing of VZV infection and the induction of immune responses in aged skin cells. |
format | Online Article Text |
id | pubmed-4742108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-47421082016-04-04 Insights into the role of immunosenescence during varicella zoster virus infection (shingles) in the aging cell model Kim, Ji-Ae Park, Seul-Ki Kumar, Mukesh Lee, Chan-Hee Shin, Ok Sarah Oncotarget Research Paper: Gerotarget (Focus on Aging) Varicella zoster virus (VZV) is the etiological agent of shingles, a painful skin rash that affects a significant proportion of the elderly population. In the present study, we used two aging cell models, Hutchinson-Gilford progeria syndrome (HGPS) fibroblasts and stress or replicative senescence-induced normal human dermal fibroblasts (NHDFs), to investigate age-associated susceptibility to VZV infection. VZV infectivity titers were significantly associated with donor age in HGPS fibroblasts and senescence induction in NHDFs. High throughput RNA-sequencing (RNA-seq) analysis was performed to assess global and dynamic changes in the host transcriptomes of VZV-infected aging cells. Analysis of differentially expressed genes (DEGs) indicated that VZV infection in aged HGPS fibroblasts resembled that in senescent NHDFs, particularly in terms of genes associated with pattern recognition receptors in virus sensing network, providing novel insights into the mechanisms of senescence-associated susceptibility to VZV infection. Additionally, we identified stimulator of interferon genes (STING) as a potential VZV sensing receptor. Knockdown of STING expression resulted in increased viral replication in primary fibroblasts, whereas STING overexpression led to suppression of VZV plaque formation. In conclusion, our findings highlight the important role of immunosenescence following VZV infection and provide significant insights into the mechanisms underlying cellular sensing of VZV infection and the induction of immune responses in aged skin cells. Impact Journals LLC 2015-10-14 /pmc/articles/PMC4742108/ /pubmed/26473290 Text en Copyright: © 2015 Kim et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper: Gerotarget (Focus on Aging) Kim, Ji-Ae Park, Seul-Ki Kumar, Mukesh Lee, Chan-Hee Shin, Ok Sarah Insights into the role of immunosenescence during varicella zoster virus infection (shingles) in the aging cell model |
title | Insights into the role of immunosenescence during varicella zoster virus infection (shingles) in the aging cell model |
title_full | Insights into the role of immunosenescence during varicella zoster virus infection (shingles) in the aging cell model |
title_fullStr | Insights into the role of immunosenescence during varicella zoster virus infection (shingles) in the aging cell model |
title_full_unstemmed | Insights into the role of immunosenescence during varicella zoster virus infection (shingles) in the aging cell model |
title_short | Insights into the role of immunosenescence during varicella zoster virus infection (shingles) in the aging cell model |
title_sort | insights into the role of immunosenescence during varicella zoster virus infection (shingles) in the aging cell model |
topic | Research Paper: Gerotarget (Focus on Aging) |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742108/ https://www.ncbi.nlm.nih.gov/pubmed/26473290 |
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