Abstract
Recently, two candidate analogs for human syncytin, denoted syncytins A and B, were identified in the murine genome. These were found to have expression patterns and functions similar to human syncytin. In addition, the identification of glial cells missing (GCM)-binding motifs in putative promoter regions of the mouse syncytins imply analogous regulation. Transcriptional modulation of syncytin by exogenous agents was recently suggested by studies reporting transactivation of syncytin in human cell lines following virus infections. The authors report that influenza A virus infection increased the levels of transcripts encoding Gcm1 and syncytin B, but not syncytin A, in NIH-3T3 cells as well as in mouse primary neurons or glia. Overexpression of human GCM1 in NIH-3T3 cells resulted in increased levels of transcripts encoding syncytin B but not syncytin A. Systemic administration of neurotropic influenza A virus resulted in a neuronal infection and increased levels of Gcm1-encoding transcripts in brains of young mice. The mouse may therefore be useful for studies on the expression and function of endogenous retroviral envelope genes and transcription factors regulating their expression in the placenta and brain during physiological or pathological conditions.
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Akiyama Y, Hosoya T, Poole AM, Hotta Y (1996). The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals. Proc Natl Acad Sci U S A 93: 14912–14916.
Antony JM, van Marle G, Opii W, Butterfield DA, Mallet F, Yong VW, Wallace JL, Deacon RM, Warren K, Power C (2004). Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination. Nat Neurosci 7: 1088–1095.
Aronsson F, Karlsson H, Ljunggren HG, Kristensson K (2001). Persistence of the influenza A/WSN/33 virus RNA at midbrain levels of immunodefective mice. J NeuroVirol 7: 117–124.
Asp L, Beraki S, Aronsson F, Rosvall L, Ogren SO, Kristensson K, Karlsson H (2005). Gene expression changes in brains of mice exposed to a maternal virus infection. Neuroreport 16: 1111–1115.
Blond JL, Lavillette D, Cheynet V, Bouton O, Oriol G, Chapel-Fernandes S, Mandrand B, Mallet F, Cosset FL (2000). An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J Virol 74: 3321–3329.
Chang CW, Chuang HC, Yu C, Yao TP, Chen H (2005). Stimulation of GCMa transcriptional activity by cyclic AMP/protein kinase A signaling is attributed to CBP-mediated acetylation of GCMa. Mol Cell Biol 25: 8401–8414.
Cheng YH, Handwerger S (2005). A placenta-specific enhancer of the human syncytin gene. Biol Reprod 73: 500–509.
Cross JC, Anson-Cartwright L, Scott IC (2002). Transcription factors underlying the development and endocrine functions of the placenta. Recent Prog Horm Res 57: 221–234.
Dupressoir A, Marceau G, Vernochet C, Benit L, Kanellopoulos C, Sapin V, Heidmann T (2005). Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae. Proc Natl Acad Sci U S A 102: 725–730.
Hosoya T, Takizawa K, Nitta K, Hotta Y (1995). Glial cells missing: a binary switch between neuronal and glial determination in Drosophila. Cell 82: 1025–1036.
Iwasaki Y, Hosoya T, Takebayashi H, Ogawa Y, Hotta Y, Ikenaka K (2003). The potential to induce glial differentiation is conserved between Drosophila and mammalian glial cells missing genes. Development 130: 6027–6035.
Jones BW, Fetter RD, Tear G, Goodman CS (1995). Glial cells missing: a genetic switch that controls glial versus neuronal fate. Cell 82: 1013–1023.
Keith JC Jr, Pijnenborg R, Van Assche FA (2002). Placental syncytin expression in normal and preeclamptic pregnancies. Am J Obstet Gynecol 187: 1122–1123; author reply 1123–1124.
Knerr I, Beinder E, Rascher W (2002). Syncytin, a novel human endogenous retroviral gene in human placenta: evidence for its dysregulation in preeclampsia and HELLP syndrome. Am J Obstet Gynecol 186: 210–213.
Knerr I, Schubert SW, Wich C, Amann K, Aigner T, Vogler T, Jung R, Dotsch J, Rascher W, Hashemolhosseini S (2005). Stimulation of GCMa and syncytin via cAMP mediated PKA signaling in human trophoblastic cells under normoxic and hypoxic conditions. FEBS Lett 579: 3991–3998.
Kudo Y, Boyd CA, Sargent IL, Redman CW (2003). Hypoxia alters expression and function of syncytin and its receptor during trophoblast cell fusion of human placental BeWo cells: implications for impaired trophoblast syncytialisation in pre-eclampsia. Biochim Biophys Acta 1638: 63–71.
Lavillette D, Marin M, Ruggieri A, Mallet F, Cosset FL, Kabat D (2002). The envelope glycoprotein of human endogenous retrovirus type W uses a divergent family of amino acid transporters/cell surface receptors. J Virol 76: 6442–6452.
Lee X, Keith JC Jr, Stumm N, Moutsatsos I, McCoy JM, Crum CP, Genest D, Chin D, Ehrenfels C, Pijnenborg R, van Assche FA, Mi S (2001). Downregulation of placental syncytin expression and abnormal protein localization in pre-eclampsia. Placenta 22: 808–812.
Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402–408.
Matouskova M, Blazkova J, Pajer P, Pavlicek A, Hejnar J (2006). CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues. Exp Cell Res 312: 1011–1020.
Mi S, Lee X, Li X, Veldman GM, Finnerty H, Racie L, LaVallie E, Tang XY, Edouard P, Howes S, Keith JC Jr, McCoy JM (2000). Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403: 785–789.
Nellaker C, Yao Y, Jones-Brando L, Mallet F, Yolken RH, Karlsson H (2006). Transactivation of elements in the human endogenous retrovirus W family by viral infection. Retrovirology 3: 44.
Owe-Larsson B, Kristensson K, Hill RH, Brodin L (1997). Distinct effects of clostridial toxins on activity-dependent modulation of autaptic responses in cultured hippocampal neurons. Eur J Neurosci 9: 1773–1777.
Perron H, Lazarini F, Ruprecht K, Péchoux-Longin C, Seilhean D, Sazdovitch V, Créange A, Battail-Poirot N, Sibaï G, Santoro L, Jolivet M, Darlix J-L, Rieckmann P, Arzberger T, Hauw J-J, 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.
Prudhomme S, Oriol G, Mallet F (2004). A retroviral promoter and a cellular enhancer define a bipartite element which controls env ERVWE1 placental expression. J Virol 78: 12157–12168.
Reinacher M, Bonin J, Narayan O, Scholtissek C (1983). Pathogenesis of neurovirulent influenza A virus infection in mice. Route of entry of virus into brain determines infection of different populations of cells. Lab Invest 49: 686–692.
Ruprecht K, Obojes K, Wengel V, Gronen F, Kim KS, Perron H, Schneider-Schaulies J, Rieckmann P (2006). Regulation of human endogenous retrovirus W protein expression by herpes simplex virus type 1: implications for multiple sclerosis. J NeuroVirol 12: 65–71.
Schreiber J, Riethmacher-Sonnenberg E, Riethmacher D, Tuerk EE, Enderich J, Bosl MR, Wegner M (2000). Placental failure in mice lacking the mammalian homolog of glial cells missing, GCMa. Mol Cell Biol 20: 2466–2474.
Schreiber J, Sock E, Wegner M (1997). The regulator of early gliogenesis glial cells missing is a transcription factor with a novel type of DNA-binding domain. Proc Natl Acad Sci U S A 94: 4739–4744.
Seamon K, Daly JW (1981). Activation of adenylate cyclase by the diterpene forskolin does not require the guanine nucleotide regulatory protein. J Biol Chem 256: 9799–9801.
Tobita K, Sugiura A, Enomote C, Furuyama M (1975). Plaque assay and primary isolation of influenza A viruses in an established line of canine kidney cells (MDCK) in the presence of trypsin. Med Microbiol Immunol (Berl) 162: 9–14.
Voisset C, Blancher A, Perron H, Mandrand B, Mallet F, Paranhos-Baccala G (1999). Phylogeny of a novel family of human endogenous retrovirus sequences, HERV-W, in humans and other primates. AIDS Res Hum Retroviruses 15: 1529–1533.
Voisset C, Bouton O, Bedin F, Duret L, Mandrand B, Mallet F, Paranhos-Baccala G (2000). Chromosomal distribution and coding capacity of the human endogenous retrovirus HERV-W family. AIDS Res Hum Retroviruses 16: 731–740.
Yu C, Shen K, Lin M, Chen P, Lin C, Chang GD, Chen H (2002). GCMa regulates the syncytin-mediated trophoblastic fusion. J Biol Chem 277: 50062–50068.
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This work was supported by the Stanley Medical Research Institute, the Swedish Research Council (project no. K2006-21X-20047-01-3), and Stiftelsen Goljes Minne (project no. 206/05).
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Asp, L., Nellåker, C. & Karlsson, H. Influenza A virus transactivates the mouse envelope gene encoding syncytin B and its regulator, glial cells missing 1. Journal of NeuroVirology 13, 29–37 (2007). https://doi.org/10.1080/13550280601103125
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DOI: https://doi.org/10.1080/13550280601103125