title: ORF3 of Hepatitis E Virus Inhibits the Expression of Proinflammatory Cytokines and Chemotactic Factors in LPS-Stimulated Human PMA-THP1 Cells by Inhibiting NF-κB Pathway.
abstract: Hepatitis E virus (HEV) is one of the primary causative agents of acute hepatitis. It is noteworthy that HEV can develop chronic infection and even lead to liver cirrhosis; however, the mechanism has not been revealed. In this study, the ELISA assay was used to detect protein levels, and we found that HEV open reading frame 3 (ORF3) protein inhibited the expression of proinflammatory cytokines (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-1β, IL-6, IL-8, IL-12p40, and IL-18) and chemotactic factors (nitric oxide [NO], interferon-inducible protein-10 (IP-10), macrophage inflammatory protein (MIP)-1α, monocyte chemoattractant protein-1 (MCP-1), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF)] in lipopolysaccharide (LPS)-stimulated human PMA-THP1 cells. Further study showed that mRNA and protein levels of pattern recognition receptors (PRRs), such as Toll-like receptor 4 (TLR4), TNF receptor-associated factor 6 (TRAF6), and nucleotide-binding oligomerization domain containing 2 (NOD2), decreased after infection of pLL3.7-ORF3 (pORF3); moreover, the inhibition produced corresponding upregulation of IκBα and downregulation of phosphorylated IκB kinase IKKɛ (p-IKKɛ) and phosphorylated nuclear factor (NF)-κB (p-NF-κB), but little variation was found in the concentration of IKKɛ and NF-κB. Taken together, our results demonstrated that HEV ORF3 attenuated LPS-induced cytokine production and chemotactic factors, predominantly by inhibiting various PRRs-mediated NF-κB signaling pathways. The anti-inflammatory properties might be of great importance to clarify the role and mechanism of macrophages in chronic HEV infection and cirrhosis.
authors.affiliation: Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China .
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Lei
authors.affiliation: Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China .
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China .
authors.forename: Jia
authors.initials: J
authors.lastname: Cai
authors.affiliation: Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China .
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Huang
authors.affiliation: Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China .
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
authors.affiliation: Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China .
authors.forename: Shujun
authors.initials: S
authors.lastname: Zhang
mesh_terms: D002460:Cell Line; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors*; D016207:Cytokines / Q000037:antagonists & inhibitors*; D020869:Gene Expression Profiling; D016752:Hepatitis E virus / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D057131:Immune Evasion; D008070:Lipopolysaccharides / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D020543:Proteome / Q000032:analysis; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D002630:Chemotactic Factors; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; C400973:ORF3 protein, Hepatitis E virus; D020543:Proteome; D014764:Viral Proteins