View : 19 Download: 0

Reactive oxygen species-induced parthanatos of immunocytes by human cytomegalovirus-associated substance

Title
Reactive oxygen species-induced parthanatos of immunocytes by human cytomegalovirus-associated substance
Authors
Kim J.H.Kim J.Roh J.Park C.-S.Seoh J.-Y.Hwang E.-S.
Ewha Authors
서주영
SCOPUS Author ID
서주영scopus
Issue Date
2018
Journal Title
Microbiology and Immunology
ISSN
0385-5600JCR Link
Citation
Microbiology and Immunology vol. 62, no. 4, pp. 229 - 242
Keywords
human cytomegalovirusparthanatosreactive oxygen species
Publisher
Blackwell Publishing Asia
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Previous studies have examined various immune evasion strategies of human cytomegalovirus (HCMV) to gain understanding of its pathogenesis. Although the mechanism that underlies immunocyte destruction near HCMV-infected lesions has yet to be established, it is here shown that substances produced by HCMV-infected cells induce death in several types of immunocytes, but not in fibroblasts or astrocytomas. These substances contain HCMV proteins and were termed HCMV-associated insoluble substance (HCMVAIS). The mechanism by which HCMVAIS induces cell death was characterized to improve understanding the death of immunocytes near HCMV-infected lesions. HCMVAIS were found to trigger production of intracellular nicotinamide adenine dinucleotide phosphate oxidase-derived reactive oxygen species (ROS), resulting in cell death, this effect being reversed following treatment with ROS inhibitors. Cell death was not induced in splenocytes from NOX-2 knockout mice. It was hypothesized that DNA damage induced by oxidative stress initiates poly ADP-ribose polymerase-1 (PARP-1)-mediated cell death, or parthanatos. HCMVAIS-induced cell death is accompanied by PARP-1 activation in a caspase-independent manner, nuclear translocation of apoptosis-inducing factor (AIF), and DNA fragmentation, which are typical features of parthanatos. Treatment with an AIF inhibitor decreased the rate of HCMVAIS-induced cell death, this being confirmed by hematoxylin and eosin staining; cell death in most HCMV-positive foci in serial section samples of a large intestine with HCMV infection was TUNEL-positive, cleaved caspase 3-negative and CD45-positive. Taken together, these data suggest that HCMV inhibits local immune responses via direct killing of immunocytes near HCMV-infected cells through ROS-induced parthanatos by HCMVAIS. © 2018 The Authors. Microbiology and Immunology published by The Societies and John Wiley & Sons Australia, Ltd
DOI
10.1111/1348-0421.12575
Appears in Collections:
의과대학 > 의학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE