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

Ji Ae Kim, Seul Ki Park, Mukesh Kumar, Chan Hee Lee, Ok Sarah Shin

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 senescenceassociated 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.

Original languageEnglish
Pages (from-to)35324-35343
Number of pages20
JournalOncotarget
Volume6
Issue number34
DOIs
Publication statusPublished - 2015

Keywords

  • Gerotarget
  • Immunosenescence
  • Progeria
  • STING
  • Shingles
  • VZV

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Insights into the role of immunosenescence during varicella zoster virus infection (shingles) in the aging cell model'. Together they form a unique fingerprint.

  • Cite this