title: Histone deacetylase inhibition by Japanese encephalitis virus in monocyte/macrophages: a novel viral immune evasion strategy.
abstract: Japanese encephalitis virus (JEV) is a common cause of encephalitis in humans who are dead-end hosts producing negligible viremia. The virus reaches the brain and causes massive inflammation. Our study seeks to understand the virus-host interaction using the murine monocyte/macrophage cell line RAW264.7, an antigen presenting cell involved in eliciting an innate immune response. We have discovered several interesting phenomena occurring in JEV-infected RAW264.7 cells which diverge from established observations. JEV remains inside RAW264.7 and appears to have little negative effect on cell viability. Expression studies of major histocompatibility complexes (MHC) and co-stimulatory molecules show inhibition of antigen presentation. There is enhanced immune suppression creating an anti-viral milieu. Expression of pro-inflammatory cytokines and chemokines is suppressed along with increased expression of anti-inflammatory molecules. Histone deacetylases (HDACs) have known inflammatory properties. In our study, through modulation of HDACs JEV seems to induce a crucial anti-inflammatory and anti-viral role in host macrophages.
authors.affiliation: National Brain Research Centre, Manesar, Haryana 122051, India.
authors.forename: Dwaipayan
authors.initials: D
authors.lastname: Adhya
authors.forename: Kallol
authors.initials: K
authors.lastname: Dutta
authors.forename: Kiran
authors.initials: K
authors.lastname: Kundu
authors.forename: Anirban
authors.initials: A
authors.lastname: Basu
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D004660:Encephalitis / Q000276:immunology*; D004664:Encephalitis Virus, Japanese / Q000276:immunology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007372:Interferons / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D051379:Mice
chemical_list: D006657:Histones; D018836:Inflammation Mediators; D002392:Catechin; D007372:Interferons; C045651:epigallocatechin gallate; D006655:Histone Deacetylases
keywords: APC; Antigen presentation; CCL-2; EGCG; HDAC; Histone deacetylase; IDO; IFN; IL-6; IRF3; Immune evasion; Inflammation; Interferon; Interferon regulatory factor 3; JEV; Japanese encephalitis virus; MHC; Macrophage; NFκB; P38MAPK; RSAD2; STAT1; TNFα; VPA; antigen-presenting cell; chemokine (C-C motif) ligand 2; epigallocatechin gallate; histone deacetylase; indoleamine 2,3-dioxygenase; interferon; interleukin 6; major histocompatibility complex; nuclear factor kappa B; p38 mitogen-activated protein kinases; radical S-adenosyl methionine domain-containing protein 2; signal transducer and activator of transcription 1; tumor necrosis factor-alpha; valproic acid