Translocating lipopolysaccharide correlates with the severity of enterovirus A71-induced HFMD by promoting pro-inflammation and viral IRES activity

Abstract Background The increase of inflammation-inducing enterobacteria was recently observed in severe hand, foot, and mouth disease (HFMD) caused by Enterovirus A71 (EV-A71). This study aimed to verify the occurrence of bacterial translocation (BT) and further explore the contributory role of BT...

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Autores principales:	Yuya Wang, Kena Dan, Xiaoling Xue, Xiongbo Yang, Xujiao Feng, Qingqing Yang, Jing Yang, Bangtao Chen
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Hand, foot, and mouth disease Enterovirus A71 2A protease (2Apro) Lipopolysaccharide Inflammation Internal ribosomal entry site (IRES) Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/92523fae1399419fa4ccd322b0e85695
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spelling	oai:doaj.org-article:92523fae1399419fa4ccd322b0e856952021-11-28T12:14:05ZTranslocating lipopolysaccharide correlates with the severity of enterovirus A71-induced HFMD by promoting pro-inflammation and viral IRES activity10.1186/s13099-021-00465-x1757-4749https://doaj.org/article/92523fae1399419fa4ccd322b0e856952021-11-01T00:00:00Zhttps://doi.org/10.1186/s13099-021-00465-xhttps://doaj.org/toc/1757-4749Abstract Background The increase of inflammation-inducing enterobacteria was recently observed in severe hand, foot, and mouth disease (HFMD) caused by Enterovirus A71 (EV-A71). This study aimed to verify the occurrence of bacterial translocation (BT) and further explore the contributory role of BT to severity of EV-A71-mediated HFMD cases. Methods Serum specimens from 65 mild and 65 severe EV-A71-associated HFMD cases and 65 healthy children were collected. EV-A71 VP1 in serum, inflammatory mediators including C-reactive protein, IL-1β, IL-6, interferon-γ and tumor necrosis factor-α, BT related biomarkers including Claudin-3, intestinal fatty acid binding protein, lipopolysaccharide (LPS), soluble CD14 (sCD14) and endotoxin core antibody were measured by ELISA. Bacterial DNA (BactDNA) fragments were quantified by quantified PCR (qPCR). Rhabdomyosarcoma (RD) or SH-SY5Y cells, infected with LPS-pre-incubated EV-A71 or transfected with plasmid containing viral 2Apro or mRNA containing viral internal ribosomal entry site (IRES), were post-treated with or without LPS in vitro. EV-A71 RNA and viral or cellular proteins were determined by qPCR and western blot, respectively. Results Compared to mild HFMD patients, remarkably higher inflammatory mediators as well as BT-related biomarkers except BactDNA were observed in severe HFMD cases (all P < 0.05). In severe HFMD group, circulating concentrations of LPS and sCD14 showed statistical correlations with inflammation indices (all P < 0.05), serum levels of EV-A71 VP1 were found to be positively correlated with serum LPS (r = 0.341, P = 0.005) and serum sCD14 (r = 0.458, P < 0.001). In vitro, EV-A71 attachment and internalization were only slightly promoted by LPS pre-incubation; however, EV-A71 proliferation and viral 2Apro-mediated IRES activity were significantly accelerated by LPS post-treatment. Conclusions Our results collectively indicate that gut-derived translocating LPS contributes to the severity of EV-A71-induced HFMD by driving inflammatory response and viral proliferation via viral 2Apro-mediated IRES.Yuya WangKena DanXiaoling XueXiongbo YangXujiao FengQingqing YangJing YangBangtao ChenBMCarticleHand, foot, and mouth diseaseEnterovirus A712A protease (2Apro)LipopolysaccharideInflammationInternal ribosomal entry site (IRES)Diseases of the digestive system. GastroenterologyRC799-869ENGut Pathogens, Vol 13, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hand, foot, and mouth disease Enterovirus A71 2A protease (2Apro) Lipopolysaccharide Inflammation Internal ribosomal entry site (IRES) Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Hand, foot, and mouth disease Enterovirus A71 2A protease (2Apro) Lipopolysaccharide Inflammation Internal ribosomal entry site (IRES) Diseases of the digestive system. Gastroenterology RC799-869 Yuya Wang Kena Dan Xiaoling Xue Xiongbo Yang Xujiao Feng Qingqing Yang Jing Yang Bangtao Chen Translocating lipopolysaccharide correlates with the severity of enterovirus A71-induced HFMD by promoting pro-inflammation and viral IRES activity
description	Abstract Background The increase of inflammation-inducing enterobacteria was recently observed in severe hand, foot, and mouth disease (HFMD) caused by Enterovirus A71 (EV-A71). This study aimed to verify the occurrence of bacterial translocation (BT) and further explore the contributory role of BT to severity of EV-A71-mediated HFMD cases. Methods Serum specimens from 65 mild and 65 severe EV-A71-associated HFMD cases and 65 healthy children were collected. EV-A71 VP1 in serum, inflammatory mediators including C-reactive protein, IL-1β, IL-6, interferon-γ and tumor necrosis factor-α, BT related biomarkers including Claudin-3, intestinal fatty acid binding protein, lipopolysaccharide (LPS), soluble CD14 (sCD14) and endotoxin core antibody were measured by ELISA. Bacterial DNA (BactDNA) fragments were quantified by quantified PCR (qPCR). Rhabdomyosarcoma (RD) or SH-SY5Y cells, infected with LPS-pre-incubated EV-A71 or transfected with plasmid containing viral 2Apro or mRNA containing viral internal ribosomal entry site (IRES), were post-treated with or without LPS in vitro. EV-A71 RNA and viral or cellular proteins were determined by qPCR and western blot, respectively. Results Compared to mild HFMD patients, remarkably higher inflammatory mediators as well as BT-related biomarkers except BactDNA were observed in severe HFMD cases (all P < 0.05). In severe HFMD group, circulating concentrations of LPS and sCD14 showed statistical correlations with inflammation indices (all P < 0.05), serum levels of EV-A71 VP1 were found to be positively correlated with serum LPS (r = 0.341, P = 0.005) and serum sCD14 (r = 0.458, P < 0.001). In vitro, EV-A71 attachment and internalization were only slightly promoted by LPS pre-incubation; however, EV-A71 proliferation and viral 2Apro-mediated IRES activity were significantly accelerated by LPS post-treatment. Conclusions Our results collectively indicate that gut-derived translocating LPS contributes to the severity of EV-A71-induced HFMD by driving inflammatory response and viral proliferation via viral 2Apro-mediated IRES.
format	article
author	Yuya Wang Kena Dan Xiaoling Xue Xiongbo Yang Xujiao Feng Qingqing Yang Jing Yang Bangtao Chen
author_facet	Yuya Wang Kena Dan Xiaoling Xue Xiongbo Yang Xujiao Feng Qingqing Yang Jing Yang Bangtao Chen
author_sort	Yuya Wang
title	Translocating lipopolysaccharide correlates with the severity of enterovirus A71-induced HFMD by promoting pro-inflammation and viral IRES activity
title_short	Translocating lipopolysaccharide correlates with the severity of enterovirus A71-induced HFMD by promoting pro-inflammation and viral IRES activity
title_full	Translocating lipopolysaccharide correlates with the severity of enterovirus A71-induced HFMD by promoting pro-inflammation and viral IRES activity
title_fullStr	Translocating lipopolysaccharide correlates with the severity of enterovirus A71-induced HFMD by promoting pro-inflammation and viral IRES activity
title_full_unstemmed	Translocating lipopolysaccharide correlates with the severity of enterovirus A71-induced HFMD by promoting pro-inflammation and viral IRES activity
title_sort	translocating lipopolysaccharide correlates with the severity of enterovirus a71-induced hfmd by promoting pro-inflammation and viral ires activity
publisher	BMC
publishDate	2021
url	https://doaj.org/article/92523fae1399419fa4ccd322b0e85695
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Translocating lipopolysaccharide correlates with the severity of enterovirus A71-induced HFMD by promoting pro-inflammation and viral IRES activity

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