Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase
Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS). These diseases are accompanied by immunological reactions in the central nervous system (CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter–nitric oxide (NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.
Keywordshuman endogenous retrovirus W family (HERV-W) env nitric oxide (NO) inducible nitric oxide synthase (iNOS) neuropsychological disorders microglia
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- Antony JM, Ellestad KK, Hammond R, Imaizumi K, Mallet F, Warren KG, Power C. 2007. The human endogenous retrovirus envelope glycoprotein, syncytin-1, regulates neuroinflamma-tion and its receptor expression in multiple sclerosis: a role for endoplasmic reticulum chaperones in astrocytes. J Immunol, 179: 1210–1224.CrossRefPubMedGoogle Scholar
- de Vera ME, Shapiro RA, Nussler AK, Mudgett JS, Simmons RL, Morris SJ, Billiar TR, Geller DA. 1996. Transcriptional regulation of human inducible nitric oxide synthase (NOS2) gene by cytokines: initial analysis of the human NOS2 promoter. Proc Natl Acad Sci U S A, 93: 1054–1059.CrossRefPubMedPubMedCentralGoogle Scholar
- Gimenez J, Montgiraud C, Pichon JP, Bonnaud B, Arsac M, Ruel K, Bouton O, Mallet F. 2010. Custom human endogenous retroviruses dedicated microarray identifies self-induced HERV-W family elements reactivated in testicular cancer upon methylation control. Nucleic Acids Res, 38: 2229–2246.CrossRefPubMedPubMedCentralGoogle Scholar
- Li W, Yang F, Liu Y, Gong R, Liu L, Feng Y, Hu P, Sun W, Hao Q, Kang L, Wu J, Zhu Y. 2009. Negative feedback regulation of IL-32 production by iNOS activation in response to dsRNA or influenza virus infection.Google Scholar
- Eur J Immunol, 39: 1019–1024.Google Scholar
- Mameli G, Astone V, Arru G, Marconi S, Lovato L, Serra C, Sotgiu S, Bonetti B, Dolei A. 2007. Brains and peripheral blood mononuclear cells of multiple sclerosis (MS) patients hyperexpress MS-associated retrovirus/HERV-W endogenous retrovirus, but not Human herpesvirus 6. J Gen Virol, 88: 264–274.CrossRefPubMedGoogle Scholar
- Mustafa AK, Gadalla MM, Snyder SH. 2009. Signaling by gasotransmitters. Sci Signal, 2: e2.Google Scholar
- Perron H, Garson JA, Bedin F, Beseme F, Paranhos-Baccala G, Komurian-Pradel F, Mallet F, Tuke PW, Voisset C, Blond JL, Lalande B, Seigneurin JM, Mandrand B. 1997. Molecular identification of a novel retrovirus repeatedly isolated from patients with multiple sclerosis. The Collaborative Research Group on Multiple Sclerosis. Proc Natl Acad Sci U S A, 94: 7583–7588.CrossRefPubMedGoogle Scholar
- Perron H, Germi R, Bernard C, Garcia-Montojo M, Deluen C, Farinelli L, Faucard R, Veas F, Stefas I, Fabriek BO, Van-Horssen J, Van-der-Valk P, Gerdil C, Mancuso R, Saresella M, Clerici M, Marcel S, Creange A, Cavaretta R, Caputo D, Arru G, Morand P, Lang AB, Sotgiu S, Ruprecht K, Rieckmann P, Villoslada P, Chofflon M, Boucraut J, Pelletier J, Hartung HP. 2012. Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease. Mult Scler, 18: 1721–1736.CrossRefPubMedPubMedCentralGoogle Scholar
- Perron H, Lazarini F, Ruprecht K, Pechoux-Longin C, Seilhean D, Sazdovitch V, Creange A, Battail-Poirot N, Sibai G, Santoro L, Jolivet M, Darlix JL, Rieckmann P, Arzberger T, Hauw JJ, Lassmann H. 2005. Human endogenous retrovirus (HERV)-W ENV and GAG proteins: physiological expression in human brain and pathophysiological modulation in multiple sclerosis lesions. J Neurovirol, 11: 23–33.CrossRefPubMedGoogle Scholar
- Seifarth W, Baust C, Murr A, Skladny H, Krieg-Schneider F, Blusch J, Werner T, Hehlmann R, Leib-Mosch C. 1998. Proviral structure, chromosomal location, and expression of HERV-KT47D, a novel human endogenous retrovirus derived from T47D particles. J Virol, 72: 8384–8391.PubMedPubMedCentralGoogle Scholar
- Zhang Z, Cao Z, Liu C, Li R, Wang W, Wang X. 2016. MiRNAEmbedded ShRNAs for Radiation-Inducible LGMN Knockdown and the Antitumor Effects on Breast Cancer. Plos One, 11: e163446.Google Scholar