Skip to main content

Advertisement

SpringerLink
Log in

Reduced expression of human endogenous retrovirus (HERV)-W GAG protein in the cingulate gyrus and hippocampus in schizophrenia, bipolar disorder, and depression

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

The human endogenous retrovirus (HERV)-W multicopy family was identified in human DNA from the previously characterized multiple sclerosis associated retroviral element (MSRV). Upregulation of the HERV-W POL has been reported in cerebrospinal fluid of patients with schizophrenia. The expression of capsid (GAG) protein of HERV-W was studied by immunohistochemistry and western blotting in postmortem brain tissue of the anterior cingulate cortex and hippocampal formation of normal controls and of patients with schizophrenia, bipolar disorder and major depression. A physiological expression of GAG protein was detected in neurons as well as astroglial cells in normal brain both in the anterior cingulate cortex and in the hippocampal formation. There was a statistically significant reduction of this expression in neurons and astroglial cells in brains from individuals with schizophrenia, major depression, and bipolar disorder. The results from the present study confirm that GAG protein encoded by the HERV-W multicopy gene family is expressed in cells of the central nervous system under normal conditions. Our findings of a cell type-, brain region- and disease-specific reduced expression in schizophrenia, major depression, and bipolar disorder are compatible with a pathophysiological role of HERVs in human brain disorders. The causes and biological consequences of this differential regulation will be the subject of further investigations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • DS An Y Xie IS Chen (2001) ArticleTitleEnvelope gene of the human endogenous retrovirus HERV-W encodes a functional retrovirus envelope J Virol 75 3488–3489 Occurrence Handle11238877 Occurrence Handle10.1128/JVI.75.7.3488-3489.2001 Occurrence Handle1:CAS:528:DC%2BD3MXitVGhsrY%3D

    Article  PubMed  CAS  Google Scholar 

  • JM Antony G van Marle W Opii DA Butterfield F Mallet VW Young JL Wallace RM Deacon K Warren C Power (2004) ArticleTitleHuman endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination Nat Neurosci 7 1088–1095 Occurrence Handle15452578 Occurrence Handle10.1038/nn1319 Occurrence Handle1:CAS:528:DC%2BD2cXnvVOntro%3D

    Article  PubMed  CAS  Google Scholar 

  • N Bannert R Kurth (2004) ArticleTitleRetroelements and the human genome: new perspectives on an old relation PNAS 101 14572–14579 Occurrence Handle15310846 Occurrence Handle10.1073/pnas.0404838101 Occurrence Handle1:CAS:528:DC%2BD2cXovVeqsrs%3D

    Article  PubMed  CAS  Google Scholar 

  • S Blaise N de Parseval L Benit T Heidmann (2003) ArticleTitleGenomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncitin-2, a gene conserved on primate evolution PNAS 100 13013–13018 Occurrence Handle14557543 Occurrence Handle10.1073/pnas.2132646100 Occurrence Handle1:CAS:528:DC%2BD3sXoslKms70%3D

    Article  PubMed  CAS  Google Scholar 

  • JL Blond F Beseme L Duret O Bouton F Bedin H Perron B Mandrand F Mallet (1999) ArticleTitleMolecular characterization and placental expression of HERV-W, a new human endogenous retrovirus family J Virol 73 1175–1185 Occurrence Handle9882319 Occurrence Handle1:CAS:528:DyaK1MXmtlajsg%3D%3D

    PubMed  CAS  Google Scholar 

  • JL Blond D Lavillette V Cheynet O Bouton G Oriol S Chapel-Fernandes B Mandrand F Mallet FL Cosset (2000) ArticleTitleAn 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 Occurrence Handle10708449 Occurrence Handle10.1128/JVI.74.7.3321-3329.2000 Occurrence Handle1:CAS:528:DC%2BD3cXhvVejtbs%3D

    Article  PubMed  CAS  Google Scholar 

  • P Charmley SS Beall P Concannon L Hood RA Gatti (1991) ArticleTitleFurther 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 Occurrence Handle1674514 Occurrence Handle10.1016/0165-5728(91)90193-B Occurrence Handle1:CAS:528:DyaK3MXltlegtro%3D

    Article  PubMed  CAS  Google Scholar 

  • C Dennis (2002) ArticleTitleMouse genome: a forage in the junkyard Nature 420 458–459 Occurrence Handle12466812 Occurrence Handle10.1038/420458a Occurrence Handle1:CAS:528:DC%2BD38Xpt1Wiur8%3D

    Article  PubMed  CAS  Google Scholar 

  • N De Parseval V Lazar JF Casella L Benit T Heidmann (2003) ArticleTitleSurvey of human genes of retroviral origin: identification and transcriptome of the genes with coding capacity for complete envelope proteins J Virol 77 10414–10422 Occurrence Handle12970426 Occurrence Handle10.1128/JVI.77.19.10414-10422.2003 Occurrence Handle1:CAS:528:DC%2BD3sXnsFymsbo%3D

    Article  PubMed  CAS  Google Scholar 

  • FB Dickerson JJ Boronow C Stallings AE Origoni I Ruslanova RH Yolken (2003) ArticleTitleAssociation of serum antibodies to herpes simplex virus 1 with cognitive deficits in individuals with schizophrenia Arch Gen Psychiatry 60 466–472 Occurrence Handle12742867 Occurrence Handle10.1001/archpsyc.60.5.466

    Article  PubMed  Google Scholar 

  • A Dolei C Serra G Mameli M Pugliatti G Sechi MC Cirotto G Rosati S Sotgiu (2002) ArticleTitleMultiple sclerosis-associated retrovirus (MSRV) in Sardinian MS patients Neurology 58 471–473 Occurrence Handle11839854 Occurrence Handle1:STN:280:DC%2BD387gvVCnug%3D%3D

    PubMed  CAS  Google Scholar 

  • O Frank M Giehl C Zheng R Hehlmann C Leib-Mösch W Seifarth (2005) ArticleTitleHuman endogenous retrovirus expression profiles in samples from brains of patients with schizophrenia and bipolar disorder J Virol 79 10890–10901 Occurrence Handle16103141 Occurrence Handle10.1128/JVI.79.17.10890-10901.2005 Occurrence Handle1:CAS:528:DC%2BD2MXps1Gls78%3D

    Article  PubMed  CAS  Google Scholar 

  • JL Frendo D Olivier V Cheynet JL Blond O Bouton M Vidaud M Rabreau D Evain-Brion F Mallet (2003) ArticleTitleDirect involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation Mol Cell Biol 23 3566–3574 Occurrence Handle12724415 Occurrence Handle10.1128/MCB.23.10.3566-3574.2003 Occurrence Handle1:CAS:528:DC%2BD3sXjs1yhtrs%3D

    Article  PubMed  CAS  Google Scholar 

  • R Gifford M Tristem (2003) ArticleTitleThe evolution, distribution and diversity of endogenous retroviruses Virus Genes 26 291–315 Occurrence Handle12876457 Occurrence Handle10.1023/A:1024455415443 Occurrence Handle1:CAS:528:DC%2BD3sXntVWks7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • PJ Harrison GW Roberts (Eds) (2000) The neuropathology of schizophrenia Oxford University Press Oxford

    Google Scholar 

  • H Karlsson S Bachmann J Schroder J McArthur EF Torrey RH Yolken (2001) ArticleTitleRetroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia PNAS 98 4634–4639 Occurrence Handle11296294 Occurrence Handle10.1073/pnas.061021998 Occurrence Handle1:CAS:528:DC%2BD3MXjtVagu7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • I Knerr E Beinder W Rascher (2002) ArticleTitleSyncitin, a novel human endogenous retroviral gene in human placenta: evidence for its dysregulation in preeclampsia and HELLP syndrome Am J Obstr Gynecol 186 210–213 Occurrence Handle10.1067/mob.2002.119636 Occurrence Handle1:CAS:528:DC%2BD38Xit1Wnsrc%3D

    Article  CAS  Google Scholar 

  • F Komurian-Pradel G Paranhos-Baccala F Bedin A Ounanian-Paraz M Sodoyer C Ott A Rajoharison E Garcia F Mallet B Mandrand H Perron (1999) ArticleTitleMolecular cloning and characterization of MSRV-related sequences associated with retrovirus-like particles Virology 260 1–9 Occurrence Handle10405350 Occurrence Handle10.1006/viro.1999.9792 Occurrence Handle1:CAS:528:DyaK1MXktlyns7s%3D

    Article  PubMed  CAS  Google Scholar 

  • B Kornek MK Storch R Weissert E Wallstroem A Stefferl T Olsson C Linington M Schmidbauer H Lassmann (2000) ArticleTitleMultiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions Am J Pathol 157 267–276 Occurrence Handle10880396 Occurrence Handle1:STN:280:DC%2BD3czptVagsw%3D%3D

    PubMed  CAS  Google Scholar 

  • E Larsson G Anderson (1998) ArticleTitleBeneficial role of human endogenous retroviruses: facts and hypothesis Scand J Immunol 48 329–338 Occurrence Handle9790301 Occurrence Handle10.1046/j.1365-3083.1998.00428.x Occurrence Handle1:STN:280:DyaK1M%2FgsV2lsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • R Löwer K Boller B Hasenmaier C Korbmacher N Müller-Lantzsch J Löwer R Kurth (1993) ArticleTitleIdentification of human endogenous retroviruses with complex mRNA expression and particle formation PNAS 90 4480–4484 Occurrence Handle8506289 Occurrence Handle10.1073/pnas.90.10.4480

    Article  PubMed  Google Scholar 

  • R Löwer J Löwer R Kurth (1996) ArticleTitleThe viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences PNAS 93 5177–5184 Occurrence Handle8643549 Occurrence Handle10.1073/pnas.93.11.5177

    Article  PubMed  Google Scholar 

  • M Mack K Bender PM Schneider (2004) ArticleTitleDetection of retroviral antisense transcripts and promoter activity of the HERV-K(C4) insertion in the MHC class III region Immunogenetics 56 321–332 Occurrence Handle15309346 Occurrence Handle10.1007/s00251-004-0705-y Occurrence Handle1:CAS:528:DC%2BD2cXpt1Glu7g%3D

    Article  PubMed  CAS  Google Scholar 

  • S Mi X Lee X Li GM Veldman H Finnerty L Racie E LaVallie XY Tang P Edouard S Howes JC Keith SuffixJr JM McCoy (2000) ArticleTitleSyncytin is a captive retroviral envelope protein involved in human placental morphogenesis Nature 403 785–789 Occurrence Handle10693809 Occurrence Handle10.1038/35001608 Occurrence Handle1:CAS:528:DC%2BD3cXhsVWitLg%3D

    Article  PubMed  CAS  Google Scholar 

  • SM Mirsattari JB Johnston R McKenna MR Del Bigio P Orr RT Ross C Power (2001) ArticleTitleAboriginals with multiple sclerosis: HLA types and predominance of neuromyelitis optica Neurology 56 317–323 Occurrence Handle11171895 Occurrence Handle1:CAS:528:DC%2BD3MXhsFGrsrw%3D

    PubMed  CAS  Google Scholar 

  • M Mura P Murcia M Caporale TE Spencer K Nagashima A Rein M Palmarini (2004) ArticleTitleLate viral interference induced by transdominant Gag of an endogenous retrovirus PNAS 101 11117–11122 Occurrence Handle15263098 Occurrence Handle10.1073/pnas.0402877101 Occurrence Handle1:CAS:528:DC%2BD2cXmsVCmtb4%3D

    Article  PubMed  CAS  Google Scholar 

  • J Nowak D Januszkiewicz M Pernak I Liwen M Zawada J Rembowska K Nowicka K Lewandowski H Hertmanowska M Wender (2003) ArticleTitleMultiple 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 Occurrence Handle12587074 Occurrence Handle1:CAS:528:DC%2BD3sXitVCmsbY%3D

    PubMed  CAS  Google Scholar 

  • P Obermayer-Straub HP Manns (2001) ArticleTitleHepatitis C and D, retroviruses and autoimmune manifestations J Autoimmun 16 275–285 Occurrence Handle11334493 Occurrence Handle10.1006/jaut.2000.0488 Occurrence Handle1:STN:280:DC%2BD3M3jvFKmsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • H Perron B Gratacap B Lalande O Genoulaz A Laurent C Geny M Mallaret P Innocenti E Schuller P Stoebner (1992) ArticleTitleIn vitro transmission and antigenicity of a retrovirus isolated from a multiple sclerosis patient Res Virol 143 337–350 Occurrence Handle1282730 Occurrence Handle1:STN:280:ByyC38nms1A%3D

    PubMed  CAS  Google Scholar 

  • H Perron JA Garson F Bedin F Beseme G Paranhos-Baccala F Komurian-Pradel F Mallet PW Tuke C Voisset JL Blond B Lalande JM Seigneurin B Mandrand (1997) ArticleTitleMolecular identification of a novel retrovirus repeatedly isolated from patients with multiple sclerosis. The collaborative research group on multiple sclerosis PNAS 94 7583–7588 Occurrence Handle9207135 Occurrence Handle10.1073/pnas.94.14.7583 Occurrence Handle1:CAS:528:DyaK2sXksFynsLc%3D

    Article  PubMed  CAS  Google Scholar 

  • H Perron JP Perin F Rieger PM Alliel (2000) ArticleTitleParticle-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 Occurrence Handle10871789

    PubMed  Google Scholar 

  • H Perron F Lazarini K Ruprecht C Pechoux-Longin D Seilhaen V Sazdovitch A Creange N Battail-Poirot G Sibai L Santoro M Jolivet JC Darlix P Rieckmann T Arzberger JJ Hauw H Lassmann (2005) ArticleTitleHuman 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 Occurrence Handle15804956 Occurrence Handle10.1080/13550280590901741 Occurrence Handle1:CAS:528:DC%2BD2MXis12nsbg%3D

    Article  PubMed  CAS  Google Scholar 

  • PM Schneider K Witzel-Schlömp C Rittner L Zhang (2001) ArticleTitleThe endogenous retroviral insertion in the human complement C4 gene modulates the expression of homologous genes by antisense inhibition Immunogenetics 53 1–9 Occurrence Handle11261924 Occurrence Handle10.1007/s002510000288 Occurrence Handle1:CAS:528:DC%2BD3MXhsFSnt7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • W Seifarth O Frank U Zeilfelder B Spiess AD Greenwood R Hehlmann C Leib-Mösch (2005) ArticleTitleComprehensive analysis of human endogenous retrovirus transcriptional activity in human tissues with a retrovirus-specific microarray J Virol 79 341–352 Occurrence Handle15596828 Occurrence Handle10.1128/JVI.79.1.341-352.2005 Occurrence Handle1:CAS:528:DC%2BD2MXhsleksg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • JC Soares S Gershon (2000) Bipolar disorders Marcel Dekker New York

    Google Scholar 

  • S Sotgiu C Serra G Mameli M Pugliatti G Rosati G Arru A Dolei (2002) ArticleTitleMultiple sclerosis-associated retrovirus and MS prognosis: an observational study Neurology 59 1071–1073 Occurrence Handle12370465 Occurrence Handle1:STN:280:DC%2BD38nhtlKgtQ%3D%3D

    PubMed  CAS  Google Scholar 

  • P Svobod P Stein M Anger E Bernstein GJ Hannon RM Schultz (2004) ArticleTitleRNAi and expression of retrotransposons MuERV-L and IAP in preimplatation mouse embryos Dev Biol 269 276–285 Occurrence Handle10.1016/j.ydbio.2004.01.028

    Article  Google Scholar 

  • D Taruscio A Mantovani (1998) ArticleTitleHuman endogenous retroviral sequences: possible roles in reproductive physiopathology Biol Reprod 59 713–724 Occurrence Handle9746718 Occurrence Handle10.1095/biolreprod59.4.713 Occurrence Handle1:CAS:528:DyaK1cXmsVGrs7k%3D

    Article  PubMed  CAS  Google Scholar 

  • D Taruscio A Mantovani (2004) ArticleTitleFactors regulating endogenous retroviral sequences in human and mouse Cytogenet Genome Res 105 351–362 Occurrence Handle15237223 Occurrence Handle10.1159/000078208 Occurrence Handle1:CAS:528:DC%2BD2cXlsV2js7k%3D

    Article  PubMed  CAS  Google Scholar 

  • EF Torrey M Webster M Knable N Johnston RH Yolken (2000) ArticleTitleThe Stanley foundation brain collection and neuropathology consortium Schizophr Res 44 151–155 Occurrence Handle10913747 Occurrence Handle10.1016/S0920-9964(99)00192-9 Occurrence Handle1:STN:280:DC%2BD3cvlsVKgtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • M Tristem (2000) ArticleTitleIdentification and characterization of novel human endogenous retrovirus families by phylogenetic screening of the human genome mapping project database J Virol 74 3715–3730 Occurrence Handle10729147 Occurrence Handle10.1128/JVI.74.8.3715-3730.2000 Occurrence Handle1:CAS:528:DC%2BD3cXitFOltr4%3D

    Article  PubMed  CAS  Google Scholar 

  • LP Villareal (1997) ArticleTitleOn viruses, sex, and motherhood J Virol 71 859–865 Occurrence Handle8995601 Occurrence Handle1:CAS:528:DyaK2sXls1arsg%3D%3D

    PubMed  CAS  Google Scholar 

  • C Voisset O Bouton F Bedin L Duret B Mandrand F Mallet G Paranhos-Baccala (2000) ArticleTitleChromosomal distribution and coding capacity of the human endogenous retrovirus HERV-W family AIDS Res Hum Retrovir 16 731–740 Occurrence Handle10826480 Occurrence Handle10.1089/088922200308738 Occurrence Handle1:CAS:528:DC%2BD3cXktVCmtL0%3D

    Article  PubMed  CAS  Google Scholar 

  • S Wei P Charmley P Concannon (1995) ArticleTitleDNA 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 Occurrence Handle7645847 Occurrence Handle10.1111/j.1749-6632.1995.tb44528.x Occurrence Handle1:CAS:528:DyaK2MXoslOis7s%3D

    Article  PubMed  CAS  Google Scholar 

  • DA Wilkinson DL Mager JC Leong (1994) Endogenous human retroviruses NumberInSeries3 Plenum Press New York

    Google Scholar 

  • JM Yi WH Lee HM Kim HS Kim (2001) ArticleTitleIdentification of new endogenous retroviral sequences belonging to the HERV-W family in human cancer cells Intervirology 44 333–338 Occurrence Handle11805438 Occurrence Handle10.1159/000050067 Occurrence Handle1:CAS:528:DC%2BD38XmtFOjsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • JM Yi HM Kim WH Lee HS Kim (2002) ArticleTitleMolecular cloning and phylogenetic analysis of new human endogenous retrovirus HERV-W family in cancer cells Curr Microbiol 44 216–220 Occurrence Handle11821931 Occurrence Handle10.1007/s00284-001-0033-5 Occurrence Handle1:CAS:528:DC%2BD38Xht1yksrc%3D

    Article  PubMed  CAS  Google Scholar 

  • JM Yi HM Kim HS Kim (2004) ArticleTitleExpression of the human endogenous retrovirus HERV-W family in various human tissues and cancer cells J Gen Virol 85 1203–1210 Occurrence Handle15105536 Occurrence Handle10.1099/vir.0.79791-0 Occurrence Handle1:CAS:528:DC%2BD2cXktFert7g%3D

    Article  PubMed  CAS  Google Scholar 

  • RH Yolken H Karlsson F Yee NL Johnston-Wilson EF Torrey (2000) ArticleTitleEndogenous retroviruses and schizophrenia Brain Res Rev 31 193–199 Occurrence Handle10719148 Occurrence Handle10.1016/S0165-0173(99)00037-5 Occurrence Handle1:CAS:528:DC%2BD3cXhsleqtr4%3D

    Article  PubMed  CAS  Google Scholar 

  • M Zawada I Liwien M Pernak D Januszkiewicz-Lewandowska K Nowicka-Kujawska J Rembowska K Lewandowski H Hertmanowska M Wender J Nowak (2003) ArticleTitleMSRV pol sequence copy number as a potential marker of multiple sclerosis Pol J Pharmacol 55 869–875 Occurrence Handle14704480 Occurrence Handle1:CAS:528:DC%2BD2cXlsFGit7o%3D

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Brain Research and Neuropathology, Departments of Psychiatry and Pathology, Uniformed Services University of the Health Sciences, and Stanley Medical Research Institute, Bethesda, MD, U.S.A.

    S. Weis, I. C. Llenos, J. R. Dulay & L. Isler

  2. Stanley Laboratory of Developmental Neurovirology, Medical School, Johns Hopkins University, Baltimore, MD, U.S.A.

    S. Sabunciyan & R. Yolken

  3. Biomérieux, R&D, Chemin de l’Orme, 69280, Marcy L’Etoile, France

    H. Perron

Authors
  1. S. Weis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. C. Llenos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Sabunciyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. R. Dulay
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. Isler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Yolken
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. Perron
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weis, S., Llenos, I., Sabunciyan, S. et al. Reduced expression of human endogenous retrovirus (HERV)-W GAG protein in the cingulate gyrus and hippocampus in schizophrenia, bipolar disorder, and depression. J Neural Transm 114, 645–655 (2007). https://doi.org/10.1007/s00702-006-0599-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-006-0599-y

Search

Navigation