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

• Published in: Gut pathogens 2021-11, Vol.13 (1), p.69-11, Article 69
• Main Authors: Wang, Yuya, Dan, Kena, Xue, Xiaoling, Yang, Xiongbo, Feng, Xujiao, Yang, Qingqing, Yang, Jing, Chen, Bangtao
• Format: Article
• Language: English
• Subjects: 2A protease (2Apro); Antibodies; Biological response modifiers; Biomarkers; Blood; C-reactive protein; CD14 antigen; Cell culture; Cellular proteins; Coxsackievirus infections; Cytokines; Enterovirus A71; Enteroviruses; Enzyme-linked immunosorbent assay; Fatty acid-binding protein; Fatty acids; Gender; Hand, foot, and mouth disease; IL-1β; Infections; Inflammation; Interferon; Interleukin 6; Internal ribosomal entry site (IRES); Internalization; Lipopolysaccharide; Lipopolysaccharides; Mitogens; mRNA; Pathogenesis; Permeability; Proteases; Protein binding; Proteins; Rhabdomyosarcoma; RNA; Serum levels; Software; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vaccines; Variance analysis; Viral antibodies; VP1 protein; γ-Interferon
• ISSN: 1757-4749; 1757-4749
• DOI: 10.1186/s13099-021-00465-x

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. 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 2A 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. 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