Journal of NeuroVirology

, Volume 11, Issue 1, pp 23–33 | Cite as

Human endogenous retrovirus (HERV)-W ENV and GAG proteins: Physiological expression in human brain and pathophysiological modulation in multiple sclerosis lesions

  • Hervé Perron
  • Françoise Lazarini
  • Klemens Ruprecht
  • Christine Péchoux-Longin
  • Danielle Seilhean
  • Véronique Sazdovitch
  • Alain Créange
  • Nicole Battail-Poirot
  • Geneviève Sibaï
  • Lyse Santoro
  • Michel Jolivet
  • Jean-Luc Darlix
  • Peter Rieckmann
  • Thomas Arzberger
  • Jean-Jacques Hauw
  • Hans Lassmann
Article

Abstract

Antigen expression of a human endogenous retrovirus family, HERV-W, in normal human brain and multiple sclerosis lesions was studied by immunohistochemistry by three independent groups. The HERV-W multicopy family was identified in human DNA from the previously characterized multiple sclerosis-associated retroviral element (MSRV). A panel of antibodies against envelope (ENV) and capsid (GAG) antigens was tested. A physiological expression of GAG proteins in neuronal cells was observed in normal brain, whereas there was a striking accumulation of GAG antigen in axonal structures in demyelinated white matter from patients with MS. Prominent HERV-W GAG expression was also detected in endothelial cells of MS lesions from acute or actively demyelinating cases, a pattern not found in any control. A physiological expression of ENV proteins was detected in microglia in normal brain; however, a specific expression in macrophages was apparently restricted to early MS lesions. Thus, converging results from three groups confirm that GAG and ENV proteins encoded by the HERV-W multicopy gene family are expressed in cells of the central nervous system under normal conditions. Similar to HERV-W7q ENV (Syncitin), which is expressed in placenta and has been shown to have a physiological function in syncytio-trophoblast fusion, HERV-W GAG may thus also have a physiological function in human brain. This expression differs in MS lesions, which may either reflect differential regulation of inherited HERV-W copies, or expression of “infectious” MSRV copies. This is compatible with a pathophysiological role in MS, but also illustrates the ambivalence of such HERV antigens, which can be expressed in cell-specific patterns, under physiological or pathological conditions.

Keywords

brain endogenous retrovirus HERV-W immunohistology multiple sclerosis neuron Syncitin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. An DS, Xie Y, Chen IS (2001). Envelope gene of the human endogenous retrovirus HERV-W encodes a functional retrovirus envelope. J Virol 75: 3488–3489.CrossRefPubMedGoogle Scholar
  2. Berlioz C, Darlix JL (1995). An internal ribosomal entry mechanism promotes translation of murine leukemia virus gag polyprotein precursors. J Virol 69: 2214–2222.PubMedGoogle Scholar
  3. Blond JL, Beseme F, Duret L, Bouton O, Bedin F, Perron H, Mandrand B, Mallet F (1999). Molecular characterization and placental expression of HERV-W, a new human endogenous retrovirus family. J Virol 73: 1175–1185.PubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. Charmley P, Beall SS, Concannon P, Hood L, Gatti RA (1991). Further localization of a multiple sclerosis susceptibility gene on chromosome 7q using a new T cell receptor beta-chain DNA polymorphism. J Neuroimmunol 32: 231–240.CrossRefPubMedGoogle Scholar
  6. Christensen T, Pedersen L, Sorensen PD, Moller-Larsen A (2002). A transmissible human endogenous retrovirus. AIDS Res Hum Retroviruses 18: 861–866.CrossRefPubMedGoogle Scholar
  7. Contag CH, Harty JT, Plagemann PG (1989). Dual virus etiology of age-dependent poliomyelitis of mice. A potential model for human motor neuron diseases. Microb Pathog 6: 391–401.CrossRefPubMedGoogle Scholar
  8. Dolei A, Serra C, Mameli G, Pugliatti M, Sechi G, Cirotto MC, Rosati G, Sotgiu S (2002). Multiple sclerosis-associated retrovirus (MSRV) in Sardinian MS patients. Neurology 58: 471–473.PubMedGoogle Scholar
  9. Gardner M (1990). Genetic resistance to a retroviral neurologic disease in wild mice. In: Retrovirus infections of the nervous system. Oldstone M, Koprowski H (eds). Berlin: Springer-Verlag, pp 3–10.Google Scholar
  10. Girod A, Drynda A, Cosset FL, Verdier G, Ronfort C (1996). Homologous and nonhomologous retroviral recombinations are both involved in the transfer by infectious particles of defective avian leukosis virus-derived transcomplementing genomes. J Virol 70: 5651–5657.PubMedGoogle Scholar
  11. Karlsson H, Bachmann S, Schroder J, McArthur J, Torrey EF, Yolken RH (2001). Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia. Proc Natl Acad Sci U S A 98: 4634–4639.CrossRefPubMedGoogle Scholar
  12. Komurian-Pradel F, Paranhos-Baccala G, Bedin F, Ounanian-Paraz A, Sodoyer M, Ott C, Rajoharison A, Garcia E, Mallet F, Mandrand B, Perron H (1999). Molecular cloning and characterization of MSRV-related sequences associated with retrovirus-like particles. Virology 260: 1–9.CrossRefPubMedGoogle Scholar
  13. Kubo Y, Kakimi K, Higo K, Kobayashi H, Ono T, Iwama Y, Kuribayashi K, Hiai H, Adachi A, Ishimoto A (1996). Possible origin of murine AIDS (MAIDS) virus: conversion of an endogenous retroviral p12gag sequence to a MAIDS-inducing sequence by frameshift mutations. J Virol 70: 6405–6409.PubMedGoogle Scholar
  14. Lower R, Boller K, Hasenmaier B, Korbmacher C, Muller-Lantzsch N, Lower J, Kurth R (1993). Identification of human endogenous retroviruses with complex mRNA expression and particle formation. Proc Natl Acad Sci U S A 90: 4480–4484.CrossRefPubMedGoogle Scholar
  15. Lower R, Lower J, Kurth R (1996). The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences. Proc Natl Acad Sci U S A 93: 5177–5184.CrossRefPubMedGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. Mirsattari SM, Johnston JB, McKenna R, Del Bigio MR, Orr P, Ross RT, Power C (2001). Aboriginals with multiple sclerosis: HLA types and predominance of neuromyelitis optica. Neurology 56: 317–323.PubMedGoogle Scholar
  18. Montano-Hirose JA, Lafage M, Lafon M (1995). Measurement of rabies virus N protein in rabies vaccines. Res Virol 146: 217–224.CrossRefPubMedGoogle Scholar
  19. Nowak J, Januszkiewicz D, Pernak M, Liwen I, Zawada M, Rembowska J, Nowicka K, Lewandowski K, Hertmanowska H, Wender M (2003). Multiple sclerosis-associated virus-related pol sequences found both in multiple sclerosis and healthy donors are more frequently expressed in multiple sclerosis patients. J NeuroVirol 9: 112–117.PubMedGoogle Scholar
  20. 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
  21. Perron H, Gratacap B, Lalande B, Genoulaz O, Laurent A, Geny C, Mallaret M, Innocenti P, Schuller E, Stoebner P, et al (1992). In vitro transmission and antigenicity of a retrovirus isolated from a multiple sclerosis patient. Res Virol 143: 337–350.CrossRefPubMedGoogle Scholar
  22. Perron H, Perin JP, Rieger F, Alliel PM (2000). Particle-associated retroviral RNA and tandem RGH/HERV-W copies on human chromosome 7q: possible components of a ‘chain-reaction’ triggered by infectious agents in multiple sclerosis? J NeuroVirol 6: S67-S75.PubMedGoogle Scholar
  23. Sotgiu S, Serra C, Mameli G, Pugliatti M, Rosati G, Arru G, Dolei A (2002). Multiple sclerosis-associated retrovirus and MS prognosis: an observational study. Neurology 59: 1071–1073.PubMedGoogle Scholar
  24. Wei S, Charmley P, Concannon P (1995). DNA sequence and polymorphism analysis of a region of the T-cell receptor beta locus thought to contain a susceptibility gene for multiple sclerosis. Ann N Y Acad Sci 756: 307–309.CrossRefPubMedGoogle Scholar
  25. Xu L, Wrona TJ, Dudley JP (1996). Exogenous mouse mammary tumor virus (MMTV) infection induces endogenous MMTV sag expression. Virology 215: 113–123.CrossRefPubMedGoogle Scholar
  26. Yi JM, Kim HM, Kim HS (2004). Expression of the human endogenous retrovirus HERV-W family in various human tissues and cancer cells. J Gen Virol 85: 1203–1210.CrossRefPubMedGoogle Scholar
  27. Yi JM, Kim HM, Lee WH, Kim HS (2002). Molecular cloning and phylogenetic analysis of new human endogenous retrovirus HERV-W family in cancer cells. Curr Microbiol 44: 216–220.CrossRefPubMedGoogle Scholar
  28. Yi JM, Lee WH, Kim HM, Kim HS (2001). Identification of new endogenous retroviral sequences belonging to the HERV-W family in human cancer cells. Intervirology 44: 333–338.CrossRefPubMedGoogle Scholar
  29. Yolken RH, Karlsson H, Yee F, Johnston-Wilson NL, Torrey EF (2000). Endogenous retroviruses and schizophrenia. Brain Res Brain Res Rev 31: 193–199.CrossRefPubMedGoogle Scholar
  30. Zawada M, Liwien I, Pernak M, Januszkiewicz-Lewandowska D, Nowicka-Kujawska K, Rembowska J, Lewandowski K, Hertmanowska H, Wender M, Nowak J (2003). MSRV pol sequence copy number as a potential marker of multiple sclerosis. Pol J Pharmacol 55: 869–875.PubMedGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2005

Authors and Affiliations

  • Hervé Perron
    • 1
  • Françoise Lazarini
    • 2
    • 3
  • Klemens Ruprecht
    • 4
  • Christine Péchoux-Longin
    • 6
  • Danielle Seilhean
    • 2
  • Véronique Sazdovitch
    • 2
  • Alain Créange
    • 7
  • Nicole Battail-Poirot
    • 1
  • Geneviève Sibaï
    • 1
  • Lyse Santoro
    • 1
  • Michel Jolivet
    • 1
  • Jean-Luc Darlix
    • 6
  • Peter Rieckmann
    • 4
  • Thomas Arzberger
    • 5
  • Jean-Jacques Hauw
    • 2
  • Hans Lassmann
    • 8
  1. 1.Chemin de l’OrmebioMérieux, R&DMarcy L’EtoileFrance
  2. 2.INSERM U 360, Laboratoire de Neuropathologie Raymond EscourolleHôpital de la SalpêtrièreParisFrance
  3. 3.Unité de Neurovirologie et Régénération du Système NerveuxInstitut PasteurParisFrance
  4. 4.Neurologische UniversitätsklinikJulius-Maximilians-UniversitätWürzburgGermany
  5. 5.Abteilung für NeuropathologieJulius-Maximilians-UniversitätWürzburgGermany
  6. 6.Laboratoire de Virologie Humaine, ENSINSERM U 412LyonFrance
  7. 7.Service de NeurologieCHU H. MondorCréteilFrance
  8. 8.Brain Research CenterMedical University of ViennaAustria

Personalised recommendations