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Oncotarget. 2015 Nov 3;6(34):35324-43. doi: 10.18632/oncotarget.6117.

Insights into the role of immunosenescence during varicella zoster virus infection (shingles) in the aging cell model.

Author information

1
Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, Republic of Korea.
2
Department of Tropical Medicine, Medical Microbiology and Pharmacology, Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA.
3
Department of Microbiology, Chungbuk National University, Cheongju, Republic of Korea.
4
Department of Microbiology, College of Medicine, Korea University, Seoul, Republic of Korea.

Abstract

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.

KEYWORDS:

Gerotarget; STING; VZV; immunosenescence; progeria; shingles

PMID:
26473290
PMCID:
PMC4742108
DOI:
10.18632/oncotarget.6117
[Indexed for MEDLINE]
Free PMC Article

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