Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Gene Therapy
  4. Volume 25, Issue 3
  5. Article
Volume 25, Issue 3
  • ISSN: 1566-5232
  • E-ISSN: 1875-5631

Abstract

An analysis of mammalian genomes has revealed a significant number of DNA sequences with transposon or viral origin. Some of these elements encode functional proteins, repurposed during evolution to play significant physiological roles in certain tissues. Some human virus-like proteins, such as Peg10 and Arc/Arg3.1, structurally demonstrate significant similarity with Gag retroviral proteins, while others, like syncytins-1 and -2, resemble envelope viral proteins. In recent years, it has become clear that these proteins can be exploited for bioengineering 'humanized' capsid particles aimed at targeted mRNA delivery. Realizing this idea could provide efficient virus-like particles for gene therapy and address the problem of viral vector immunogenicity. This review provides an overview of the most-studied human proteins of viral or transposon origin and highlights their biological functions. Additionally, recent advances in exploiting these proteins for targeted mRNA delivery and prospects for their clinical application are discussed.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cgt/10.2174/0115665232303436240515071754
2024-05-24
2025-06-22

  • From This Site

    /content/journals/cgt/10.2174/0115665232303436240515071754
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. MonahanP.E. NégrierC. TarantinoM. ValentinoL.A. MingozziF. Emerging immunogenicity and genotoxicity considerations of adeno-associated virus vector gene therapy for hemophilia.J. Clin. Med.20211011247110.3390/jcm1011247134199563
     [Google Scholar]
  2. ShirleyJ.L. de JongY.P. TerhorstC. HerzogR.W. Immune responses to viral gene therapy vectors.Mol. Ther.202028370972210.1016/j.ymthe.2020.01.00131968213
     [Google Scholar]
  3. LanderE.S. LintonL.M. BirrenB. NusbaumC. ZodyM.C. BaldwinJ. DevonK. DewarK. DoyleM. FitzHughW. FunkeR. GageD. HarrisK. HeafordA. HowlandJ. KannL. LehoczkyJ. LeVineR. McEwanP. McKernanK. MeldrimJ. MesirovJ.P. MirandaC. MorrisW. NaylorJ. RaymondC. RosettiM. SantosR. SheridanA. SougnezC. Stange-ThomannN. StojanovicN. SubramanianA. WymanD. RogersJ. SulstonJ. AinscoughR. BeckS. BentleyD. BurtonJ. CleeC. CarterN. CoulsonA. DeadmanR. DeloukasP. DunhamA. DunhamI. DurbinR. FrenchL. GrafhamD. GregoryS. HubbardT. HumphrayS. HuntA. JonesM. LloydC. McMurrayA. MatthewsL. MercerS. MilneS. MullikinJ.C. MungallA. PlumbR. RossM. ShownkeenR. SimsS. WaterstonR.H. WilsonR.K. HillierL.W. McPhersonJ.D. MarraM.A. MardisE.R. FultonL.A. ChinwallaA.T. PepinK.H. GishW.R. ChissoeS.L. WendlM.C. DelehauntyK.D. MinerT.L. DelehauntyA. KramerJ.B. CookL.L. FultonR.S. JohnsonD.L. MinxP.J. CliftonS.W. HawkinsT. BranscombE. PredkiP. RichardsonP. WenningS. SlezakT. DoggettN. ChengJ.F. OlsenA. LucasS. ElkinC. UberbacherE. FrazierM. GibbsR.A. MuznyD.M. SchererS.E. BouckJ.B. SodergrenE.J. WorleyK.C. RivesC.M. GorrellJ.H. MetzkerM.L. NaylorS.L. KucherlapatiR.S. NelsonD.L. WeinstockG.M. SakakiY. FujiyamaA. HattoriM. YadaT. ToyodaA. ItohT. KawagoeC. WatanabeH. TotokiY. TaylorT. WeissenbachJ. HeiligR. SaurinW. ArtiguenaveF. BrottierP. BrulsT. PelletierE. RobertC. WinckerP. RosenthalA. PlatzerM. NyakaturaG. TaudienS. RumpA. SmithD.R. Doucette-StammL. RubenfieldM. WeinstockK. LeeH.M. DuboisJ.A. YangH. YuJ. WangJ. HuangG. GuJ. HoodL. RowenL. MadanA. QinS. DavisR.W. FederspielN.A. AbolaA.P. ProctorM.J. RoeB.A. ChenF. PanH. RamserJ. LehrachH. ReinhardtR. McCombieW.R. de la BastideM. DedhiaN. BlöckerH. HornischerK. NordsiekG. AgarwalaR. AravindL. BaileyJ.A. BatemanA. BatzoglouS. BirneyE. BorkP. BrownD.G. BurgeC.B. CeruttiL. ChenH-C. ChurchD. ClampM. CopleyR.R. DoerksT. EddyS.R. EichlerE.E. FureyT.S. GalaganJ. GilbertJ.G.R. HarmonC. HayashizakiY. HausslerD. HermjakobH. HokampK. JangW. JohnsonL.S. JonesT.A. KasifS. KaspryzkA. KennedyS. KentW.J. KittsP. KooninE.V. KorfI. KulpD. LancetD. LoweT.M. McLysaghtA. MikkelsenT. MoranJ.V. MulderN. PollaraV.J. PontingC.P. SchulerG. SchultzJ. SlaterG. SmitA.F.A. StupkaE. SzustakowkiJ. Thierry-MiegD. Thierry-MiegJ. WagnerL. WallisJ. WheelerR. WilliamsA. WolfY.I. WolfeK.H. YangS-P. YehR-F. CollinsF. GuyerM.S. PetersonJ. FelsenfeldA. WetterstrandK.A. MyersR.M. SchmutzJ. DicksonM. GrimwoodJ. CoxD.R. OlsonM.V. KaulR. RaymondC. ShimizuN. KawasakiK. MinoshimaS. EvansG.A. AthanasiouM. SchultzR. PatrinosA. MorganM.J. de JongP. CataneseJ.J. OsoegawaK. ShizuyaH. ChoiS. ChenY.J. SzustakowkiJ. International Human Genome Sequencing Consortium Initial sequencing and analysis of the human genome.Nature2001409682286092110.1038/3505706211237011
     [Google Scholar]
  4. Kaneko-IshinoT. IshinoF. The role of genes domesticated from LTR retrotransposons and retroviruses in mammals.Front. Microbiol.2012326210.3389/fmicb.2012.0026222866050
     [Google Scholar]
  5. LyfordG.L. YamagataK. KaufmannW.E. BarnesC.A. SandersL.K. CopelandN.G. GilbertD.J. JenkinsN.A. LanahanA.A. WorleyP.F. Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites.Neuron199514243344510.1016/0896‑6273(95)90299‑67857651
     [Google Scholar]
  6. GuzowskiJ.F. TimlinJ.A. RoysamB. McNaughtonB.L. WorleyP.F. BarnesC.A. Mapping behaviorally relevant neural circuits with immediate-early gene expression.Curr. Opin. Neurobiol.200515559960610.1016/j.conb.2005.08.01816150584
     [Google Scholar]
  7. VazdarjanovaA. Ramirez-AmayaV. InselN. PlummerT.K. RosiS. ChowdhuryS. MikhaelD. WorleyP.F. GuzowskiJ.F. BarnesC.A. Spatial exploration induces ARC, a plasticity-related immediate-early gene, only in calcium/calmodulin-dependent protein kinase II-positive principal excitatory and inhibitory neurons of the rat forebrain.J. Comp. Neurol.2006498331732910.1002/cne.2100316871537
     [Google Scholar]
  8. RodríguezJ.J. DaviesH.A. SilvaA.T. De SouzaI.E.J. PeddieC.J. ColyerF.M. LancashireC.L. FineA. ErringtonM.L. BlissT.V.P. StewartM.G. Long-term potentiation in the rat dentate gyrus is associated with enhanced Arc/Arg3.1 protein expression in spines, dendrites and glia.Eur. J. Neurosci.20052192384239610.1111/j.1460‑9568.2005.04068.x15932597
     [Google Scholar]
  9. MogaD.E. CalhounM.E. ChowdhuryA. WorleyP. MorrisonJ.H. ShapiroM.L. Activity-regulated cytoskeletal-associated protein is localized to recently activated excitatory synapses.Neuroscience2004125171110.1016/j.neuroscience.2004.02.00415051140
     [Google Scholar]
  10. BloomerW.A.C. VanDongenH.M.A. VanDongenA.M.J. Activity-regulated cytoskeleton-associated protein Arc/Arg3.1 binds to spectrin and associates with nuclear promyelocytic leukemia (PML) bodies.Brain Res.20071153203310.1016/j.brainres.2007.03.07917466953
     [Google Scholar]
  11. GuzowskiJ.F. McNaughtonB.L. BarnesC.A. WorleyP.F. Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles.Nat. Neurosci.19992121120112410.1038/1604610570490
     [Google Scholar]
  12. RodríguezJ.J. DaviesH.A. ErringtonM.L. VerkhratskyA. BlissT.V.P. StewartM.G. ARG3.1/ARC expression in hippocampal dentate gyrus astrocytes: Ultrastructural evidence and co-localization with glial fibrillary acidic protein.J. Cell. Mol. Med.200812267167810.1111/j.1582‑4934.2007.00105.x18419604
     [Google Scholar]
  13. MaierB. MedranoS. SleightS.B. ViscontiP.E. ScrableH. Developmental association of the synaptic activity-regulated protein arc with the mouse acrosomal organelle and the sperm tail.Biol. Reprod.2003681677610.1095/biolreprod.102.00414312493697
     [Google Scholar]
  14. UferF. VargasP. EnglerJ.B. TintelnotJ. SchattlingB. WinklerH. BauerS. KursaweN. WillingA. KeminerO. OhanaO. Salinas-RiesterG. PlessO. KuhlD. FrieseM.A. Arc/Arg3.1 governs inflammatory dendritic cell migration from the skin and thereby controls T cell activation.Sci. Immunol.201613eaaf866510.1126/sciimmunol.aaf866528783680
     [Google Scholar]
  15. PlathN. OhanaO. DammermannB. ErringtonM.L. SchmitzD. GrossC. MaoX. EngelsbergA. MahlkeC. WelzlH. KobalzU. StawrakakisA. FernandezE. WaltereitR. Bick-SanderA. TherstappenE. CookeS.F. BlanquetV. WurstW. SalmenB. BöslM.R. LippH.P. GrantS.G.N. BlissT.V.P. WolferD.P. KuhlD. Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories.Neuron200652343744410.1016/j.neuron.2006.08.02417088210
     [Google Scholar]
  16. NikolaienkoO. PatilS. EriksenM.S. BramhamC.R. Arc protein: A flexible hub for synaptic plasticity and cognition.Semin. Cell Dev. Biol.201877334210.1016/j.semcdb.2017.09.00628890419
     [Google Scholar]
  17. ShepherdJ.D. BearM.F. New views of Arc, a master regulator of synaptic plasticity.Nat. Neurosci.201114327928410.1038/nn.270821278731
     [Google Scholar]
  18. KorbE. FinkbeinerS. Arc in synaptic plasticity: From gene to behavior.Trends Neurosci.2011341159159810.1016/j.tins.2011.08.00721963089
     [Google Scholar]
  19. GuzowskiJ.F. LyfordG.L. StevensonG.D. HoustonF.P. McGaughJ.L. WorleyP.F. BarnesC.A. Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory.J. Neurosci.200020113993400110.1523/JNEUROSCI.20‑11‑03993.200010818134
     [Google Scholar]
  20. PeeblesC.L. YooJ. ThwinM.T. PalopJ.J. NoebelsJ.L. FinkbeinerS. Arc regulates spine morphology and maintains network stability in vivo.Proc. Natl. Acad. Sci. USA201010742181731817810.1073/pnas.100654610720921410
     [Google Scholar]
  21. MessaoudiE. KanhemaT. SouléJ. TironA. DagyteG. da SilvaB. BramhamC.R. Sustained Arc/Arg3.1 synthesis controls long-term potentiation consolidation through regulation of local actin polymerization in the dentate gyrus in vivo.J. Neurosci.20072739104451045510.1523/JNEUROSCI.2883‑07.200717898216
     [Google Scholar]
  22. WuJ. PetraliaR.S. KurushimaH. PatelH. JungM. VolkL. ChowdhuryS. ShepherdJ.D. DehoffM. LiY. KuhlD. HuganirR.L. PriceD.L. ScannevinR. TroncosoJ.C. WongP.C. WorleyP.F. Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent β-amyloid generation.Cell2011147361562810.1016/j.cell.2011.09.03622036569
     [Google Scholar]
  23. FromerM. PocklingtonA.J. KavanaghD.H. WilliamsH.J. DwyerS. GormleyP. GeorgievaL. ReesE. PaltaP. RuderferD.M. CarreraN. HumphreysI. JohnsonJ.S. RoussosP. BarkerD.D. BanksE. MilanovaV. GrantS.G. HannonE. RoseS.A. ChambertK. MahajanM. ScolnickE.M. MoranJ.L. KirovG. PalotieA. McCarrollS.A. HolmansP. SklarP. OwenM.J. PurcellS.M. O’DonovanM.C. De novo mutations in schizophrenia implicate synaptic networks.Nature2014506748717918410.1038/nature1292924463507
     [Google Scholar]
  24. PurcellS.M. MoranJ.L. FromerM. RuderferD. SolovieffN. RoussosP. O’DushlaineC. ChambertK. BergenS.E. KählerA. DuncanL. StahlE. GenoveseG. FernándezE. CollinsM.O. KomiyamaN.H. ChoudharyJ.S. MagnussonP.K.E. BanksE. ShakirK. GarimellaK. FennellT. DePristoM. GrantS.G.N. HaggartyS.J. GabrielS. ScolnickE.M. LanderE.S. HultmanC.M. SullivanP.F. McCarrollS.A. SklarP. A polygenic burden of rare disruptive mutations in schizophrenia.Nature2014506748718519010.1038/nature1297524463508
     [Google Scholar]
  25. ManagòF. MereuM. MastwalS. MastrogiacomoR. ScheggiaD. EmanueleM. De LucaM.A. WeinbergerD.R. WangK.H. PapaleoF. Genetic disruption of Arc/Arg3.1 in mice causes alterations in dopamine and neurobehavioral phenotypes related to schizophrenia.Cell Rep.20161682116212810.1016/j.celrep.2016.07.04427524619
     [Google Scholar]
  26. AlhowikanA.M. Activity-regulated cytoskeleton-associated protein dysfunction may contribute to memory disorder and earlier detection of autism spectrum disorders.Med. Princ. Pract.201625435035410.1159/00044535126967659
     [Google Scholar]
  27. ParkS. ParkJ.M. KimS. KimJ.A. ShepherdJ.D. Smith-HicksC.L. ChowdhuryS. KaufmannW. KuhlD. RyazanovA.G. HuganirR.L. LindenD.J. WorleyP.F. Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD.Neuron2008591708310.1016/j.neuron.2008.05.02318614030
     [Google Scholar]
  28. GreerP.L. HanayamaR. BloodgoodB.L. MardinlyA.R. LiptonD.M. FlavellS.W. KimT.K. GriffithE.C. WaldonZ. MaehrR. PloeghH.L. ChowdhuryS. WorleyP.F. SteenJ. GreenbergM.E. The angelman syndrome protein Ube3A regulates synapse development by ubiquitinating arc.Cell2010140570471610.1016/j.cell.2010.01.02620211139
     [Google Scholar]
  29. CaoC. Rioult-PedottiM.S. MiganiP. YuC.J. TiwariR. ParangK. SpallerM.R. GoebelD.J. MarshallJ. Impairment of TrkB-PSD-95 signaling in Angelman syndrome.PLoS Biol.2013112e1001478e100147810.1371/journal.pbio.100147823424281
     [Google Scholar]
  30. LeungH.W. FooG. VanDongenA. Arc regulates transcription of genes for plasticity, excitability and alzheimer’s disease.Biomedicines2022108194610.3390/biomedicines1008194636009494
     [Google Scholar]
  31. IchikawaH. FujimotoT. TairaE. MikiN. The accumulation of arc (an immediate early gene) mRNA by the inhibition of protein synthesis.J. Pharmacol. Sci.200391324725410.1254/jphs.91.24712686748
     [Google Scholar]
  32. MyrumC. BaumannA. BustadH.J. FlydalM.I. MariauleV. AlviraS. CuéllarJ. HaavikJ. SouléJ. ValpuestaJ.M. MárquezJ.A. MartinezA. BramhamC.R. Arc is a flexible modular protein capable of reversible self-oligomerization.Biochem. J.2015468114515810.1042/BJ2014144625748042
     [Google Scholar]
  33. AshleyJ. CordyB. LuciaD. FradkinL.G. BudnikV. ThomsonT. Retrovirus-like gag protein Arc1 binds RNA and traffics across synaptic boutons.Cell20181721-2262274.e1110.1016/j.cell.2017.12.02229328915
     [Google Scholar]
  34. VolffJ.N. Cellular genes derived from Gypsy/Ty3 retrotransposons in mammalian genomes.Ann. N. Y. Acad. Sci.20091178123324310.1111/j.1749‑6632.2009.05005.x19845640
     [Google Scholar]
  35. TaylorW.R. StoyeJ.P. TaylorI.A. A comparative analysis of the foamy and ortho virus capsid structures reveals an ancient domain duplication.BMC Struct. Biol.2018171310.1186/s12900‑017‑0073‑028372592
     [Google Scholar]
  36. EriksenM.S. BramhamC.R. Molecular physiology of Arc/Arg3.1: The oligomeric state hypothesis of synaptic plasticity.Acta Physiol.20222363e1388610.1111/apha.1388636073248
     [Google Scholar]
  37. CampillosM. DoerksT. ShahP. BorkP. Computational characterization of multiple Gag-like human proteins.Trends Genet.2006221158558910.1016/j.tig.2006.09.00616979784
     [Google Scholar]
  38. HallinE.I. EriksenM.S. BaryshnikovS. NikolaienkoO. GrødemS. HosokawaT. HayashiY. BramhamC.R. KursulaP. Structure of monomeric full-length ARC sheds light on molecular flexibility, protein interactions, and functional modalities.J. Neurochem.2018147332334310.1111/jnc.1455630028513
     [Google Scholar]
  39. EriksenM.S. NikolaienkoO. HallinE.I. GrødemS. BustadH.J. FlydalM.I. MerskiI. HosokawaT. LascuD. AkerkarS. CuéllarJ. ChambersJ.J. O’ConnellR. MuruganandamG. LorisR. ToumaC. KanhemaT. HayashiY. StrattonM.M. ValpuestaJ.M. KursulaP. MartinezA. BramhamC.R. Arc self-association and formation of virus-like capsids are mediated by an N-terminal helical coil motif.FEBS J.202128892930295510.1111/febs.1561833175445
     [Google Scholar]
  40. PastuzynE.D. DayC.E. KearnsR.B. Kyrke-SmithM. TaibiA.V. McCormickJ. YoderN. BelnapD.M. ErlendssonS. MoradoD.R. BriggsJ.A.G. FeschotteC. ShepherdJ.D. The neuronal gene arc encodes a repurposed retrotransposon gag protein that mediates intercellular RNA transfer.Cell20181721-2275288.e1810.1016/j.cell.2017.12.02429328916
     [Google Scholar]
  41. de la PeñaJ.B. Barragan-IglesiasP. LouT.F. KunderN. LoerchS. ShuklaT. BasavarajappaL. SongJ. JamesD.N. MegatS. MoyJ.K. WanghzouA. RayP.R. HoytK. StewardO. PriceT.J. ShepherdJ. CampbellZ.T. Intercellular arc signaling regulates vasodilation.J. Neurosci.202141377712772610.1523/JNEUROSCI.0440‑21.202134326146
     [Google Scholar]
  42. Al OthmanA. BagrovD. RozenbergJ.M. Retrovirus-like gag protein Arc/Arg3.1 is involved in extracellular-vesicle-mediated mRNA transfer between glioma cells.Biochim Biophys Acta Gen Subj.20241868113052210.1016/j.bbagen.2023.13052237995879
     [Google Scholar]
  43. GiorgiC. YeoG.W. StoneM.E. KatzD.B. BurgeC. TurrigianoG. MooreM.J. The EJC factor eIF4AIII modulates synaptic strength and neuronal protein expression.Cell2007130117919110.1016/j.cell.2007.05.02817632064
     [Google Scholar]
  44. PinkstaffJ.K. ChappellS.A. MauroV.P. EdelmanG.M. KrushelL.A. Internal initiation of translation of five dendritically localized neuronal mRNAs.Proc. Natl. Acad. Sci. USA20019852770277510.1073/pnas.05162339811226315
     [Google Scholar]
  45. BramhamC.R. AlmeM.N. BittinsM. KuipersS.D. NairR.R. PaiB. PanjaD. SchubertM. SouleJ. TironA. WibrandK. The Arc of synaptic memory.Exp. Brain Res.2010200212514010.1007/s00221‑009‑1959‑219690847
     [Google Scholar]
  46. ShepherdJ.D. Arc – An endogenous neuronal retrovirus?Semin. Cell Dev. Biol.201877737810.1016/j.semcdb.2017.09.02928941877
     [Google Scholar]
  47. KedrovA.V. DurymanovM. AnokhinK.V. The Arc gene: Retroviral heritage in cognitive functions.Neurosci. Biobehav. Rev.20199927528110.1016/j.neubiorev.2019.02.00630772431
     [Google Scholar]
  48. OnoR. KobayashiS. WagatsumaH. AisakaK. KohdaT. Kaneko-IshinoT. IshinoF. A retrotransposon-derived gene, PEG10, is a novel imprinted gene located on human chromosome 7q21.Genomics200173223223710.1006/geno.2001.649411318613
     [Google Scholar]
  49. SuzukiS. OnoR. NaritaT. PaskA.J. ShawG. WangC. KohdaT. AlsopA.E. Marshall GravesJ.A. KoharaY. IshinoF. RenfreeM.B. Kaneko-IshinoT. Retrotransposon silencing by DNA methylation can drive mammalian genomic imprinting.PLoS Genet.200734e55e5510.1371/journal.pgen.003005517432937
     [Google Scholar]
  50. AbedM. VerschuerenE. BudayevaH. LiuP. KirkpatrickD.S. RejaR. KummerfeldS.K. WebsterJ.D. GierkeS. ReicheltM. AndersonK.R. NewmanR.J. Roose-GirmaM. ModrusanZ. PektasH. MaltepeE. NewtonK. DixitV.M. The Gag protein PEG10 binds to RNA and regulates trophoblast stem cell lineage specification.PLoS One2019144e0214110e021411010.1371/journal.pone.021411030951545
     [Google Scholar]
  51. ShigemotoK. BrennanJ. WallsE. WatsonC.J. StottD. RigbyP.W.J. ReithA.D. Identification and characterisation of a developmentally regulated mammalian gene that utilises –1 programmed ribosomal frameshifting.Nucleic Acids Res.200129194079408810.1093/nar/29.19.407911574691
     [Google Scholar]
  52. OnoR. NakamuraK. InoueK. NaruseM. UsamiT. Wakisaka-SaitoN. HinoT. Suzuki-MigishimaR. OgonukiN. MikiH. KohdaT. OguraA. YokoyamaM. Kaneko-IshinoT. IshinoF. Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality.Nat. Genet.200638110110610.1038/ng169916341224
     [Google Scholar]
  53. ShiuraH. OnoR. TachibanaS. KohdaT. Kaneko-IshinoT. IshinoF. PEG10 viral aspartic protease domain is essential for the maintenance of fetal capillary structure in the mouse placenta.Development202114819dev19956410.1242/dev.19956434559199
     [Google Scholar]
  54. OkabeH. SatohS. FurukawaY. KatoT. HasegawaS. NakajimaY. YamaokaY. NakamuraY. Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1.Cancer Res.200363123043304812810624
     [Google Scholar]
  55. AkamatsuS. WyattA.W. LinD. LysakowskiS. ZhangF. KimS. TseC. WangK. MoF. HaegertA. BrahmbhattS. BellR. AdomatH. KawaiY. XueH. DongX. FazliL. TsaiH. LotanT.L. KossaiM. MosqueraJ.M. RubinM.A. BeltranH. ZoubeidiA. WangY. GleaveM.E. CollinsC.C. The placental gene PEG10 promotes progression of neuroendocrine prostate cancer.Cell Rep.201512692293610.1016/j.celrep.2015.07.01226235627
     [Google Scholar]
  56. LiC.M. MargolinA.A. SalasM. MemeoL. MansukhaniM. HibshooshH. SzabolcsM. KlinakisA. TyckoB. PEG10 is a c-MYC target gene in cancer cells.Cancer Res.200666266567210.1158/0008‑5472.CAN‑05‑155316423995
     [Google Scholar]
  57. XieT. PanS. ZhengH. LuoZ. TemboK.M. JamalM. YuZ. YuY. XiaJ. YinQ. WangM. YuanW. ZhangQ. XiongJ. PEG10 as an oncogene: Expression regulatory mechanisms and role in tumor progression.Cancer Cell Int.201818111210.1186/s12935‑018‑0610‑330123090
     [Google Scholar]
  58. ClarkM.B. JänickeM. GottesbührenU. KleffmannT. LeggeM. PooleE.S. TateW.P. Mammalian gene PEG10 expresses two reading frames by high efficiency -1 frameshifting in embryonic-associated tissues.J. Biol. Chem.200728252373593736910.1074/jbc.M70567620017942406
     [Google Scholar]
  59. LuxH. FlammannH. HafnerM. LuxA. Genetic and molecular analyses of PEG10 reveal new aspects of genomic organization, transcription and translation.PLoS One201051e8686e868610.1371/journal.pone.000868620084274
     [Google Scholar]
  60. ZurowskaK. AlamA. Ganser-PornillosB.K. PornillosO. Structural evidence that MOAP1 and PEG10 are derived from retrovirus/retrotransposon Gag proteins.Proteins202290130931310.1002/prot.2620434357660
     [Google Scholar]
  61. SegelM LashB SongJ Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery. Science 2021373197988288910.1126/science.abg6155
     [Google Scholar]
  62. LokossouA. ToudicC. BarbeauB. Implication of human endogenous retrovirus envelope proteins in placental functions.Viruses20146114609462710.3390/v611460925421890
     [Google Scholar]
  63. BlaiseS. de ParsevalN. BénitL. HeidmannT. Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution.Proc. Natl. Acad. Sci. USA200310022130131301810.1073/pnas.213264610014557543
     [Google Scholar]
  64. RuigrokK. VaneyM.C. BuchrieserJ. BaqueroE. HellertJ. BaronB. EnglandP. SchwartzO. ReyF.A. BackovicM. X-ray structures of the post-fusion 6-helix bundle of the human syncytins and their functional implications.J. Mol. Biol.2019431244922494010.1016/j.jmb.2019.10.02031711961
     [Google Scholar]
  65. MalassinéA. BlaiseS. HandschuhK. LalucqueH. DupressoirA. Evain-BrionD. HeidmannT. Expression of the fusogenic HERV-FRD Env glycoprotein (syncytin 2) in human placenta is restricted to villous cytotrophoblastic cells.Placenta2007282-318519110.1016/j.placenta.2006.03.00116714059
     [Google Scholar]
  66. MuirA. LeverA.M.L. MoffettA. Human endogenous retrovirus-W envelope (syncytin) is expressed in both villous and extravillous trophoblast populations.J. Gen. Virol.20068772067207110.1099/vir.0.81412‑016760410
     [Google Scholar]
  67. MiS. LeeX. LiX. VeldmanG.M. FinnertyH. RacieL. LaVallieE. TangX.Y. EdouardP. HowesS. KeithJ.C.Jr McCoyJ.M. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis.Nature2000403677178578910.1038/3500160810693809
     [Google Scholar]
  68. TrejbalováK. BlažkováJ. MatouškováM. KučerováD. PecnováL. VernerováZ. HeráčekJ. HirschI. HejnarJ. Epigenetic regulation of transcription and splicing of syncytins, fusogenic glycoproteins of retroviral origin.Nucleic Acids Res.201139208728873910.1093/nar/gkr56221771862
     [Google Scholar]
  69. LiangC.Y. WangL.J. ChenC.P. ChenL.F. ChenY.H. ChenH. GCM1 regulation of the expression of syncytin 2 and its cognate receptor MFSD2A in human placenta.Biol. Reprod.201083338739510.1095/biolreprod.110.08391520484742
     [Google Scholar]
  70. LavialleC. CornelisG. DupressoirA. EsnaultC. HeidmannO. VernochetC. HeidmannT. Paleovirology of ‘ syncytins ’, retroviral env genes exapted for a role in placentation.Philos. Trans. R. Soc. Lond. B Biol. Sci.201336816262012050710.1098/rstb.2012.050723938756
     [Google Scholar]
  71. BenirschkeK. KaufmannP. Pathology of the human placenta.4th edNew YorkSpringer200010.1007/978‑1‑4757‑4199‑5
     [Google Scholar]
  72. BischofP. Irminger-FingerI. The human cytotrophoblastic cell, a mononuclear chameleon.Int. J. Biochem. Cell Biol.200537116
     [Google Scholar]
  73. BjerregaardB. HolckS. ChristensenI.J. LarssonL.I. Syncytin is involved in breast cancer-endothelial cell fusions.Cell. Mol. Life Sci.200663161906191110.1007/s00018‑006‑6201‑916871371
     [Google Scholar]
  74. StrisselP.L. RuebnerM. ThielF. WachterD. EkiciA.B. WolfF. ThiemeF. RuprechtK. BeckmannM.W. StrickR. Reactivation of codogenic endogenous retroviral (ERV) envelope genes in human endometrial carcinoma and prestages: Emergence of new molecular targets.Oncotarget20123101204121910.18632/oncotarget.67923085571
     [Google Scholar]
  75. SunY. OuyangD.Y. PangW. TuY.Q. LiY.Y. ShenX.M. TamS.C. YangH.Y. ZhengY.T. Expression of syncytin in leukemia and lymphoma cells.Leuk. Res.20103491195120210.1016/j.leukres.2010.03.01620362331
     [Google Scholar]
  76. LarsenJ.M. ChristensenI.J. NielsenH.J. HansenU. BjerregaardB. TaltsJ.F. LarssonL.I. Syncytin immunoreactivity in colorectal cancer: Potential prognostic impact.Cancer Lett.20092801444910.1016/j.canlet.2009.02.00819327884
     [Google Scholar]
  77. LarssonL.I. HolckS. ChristensenI.J. Prognostic role of syncytin expression in breast cancer.Hum. Pathol.200738572673110.1016/j.humpath.2006.10.01817306327
     [Google Scholar]
  78. LiuC. XuJ. WenF. YangF. LiX. GengD. LiL. ChenJ. ZhengJ. Upregulation of syncytin-1 promotes invasion and metastasis by activating epithelial-mesenchymal transition-related pathway in endometrial carcinoma.OncoTargets Ther.201812314010.2147/OTT.S19104130588028
     [Google Scholar]
  79. AntonyJ.M. EllestadK.K. HammondR. ImaizumiK. MalletF. WarrenK.G. PowerC. The human endogenous retrovirus envelope glycoprotein, syncytin-1, regulates neuroinflammation and its receptor expression in multiple sclerosis: A role for endoplasmic reticulum chaperones in astrocytes.J. Immunol.200717921210122410.4049/jimmunol.179.2.121017617614
     [Google Scholar]
  80. HuangW. LiS. HuY. YuH. LuoF. ZhangQ. ZhuF. Implication of the env gene of the human endogenous retrovirus W family in the expression of BDNF and DRD3 and development of recent-onset schizophrenia.Schizophr. Bull.2011375988100010.1093/schbul/sbp16620100784
     [Google Scholar]
  81. GarsonJ.A. TukeP.W. GiraudP. Paranhos-BaccalaG. PerronH. Detection of virion-associated MSRV-RNA in serum of patients with multiple sclerosis.Lancet199835190953310.1016/S0140‑6736(98)24001‑39433428
     [Google Scholar]
  82. WangX. HuangJ. ZhuF. Human endogenous retroviral envelope protein syncytin-1 and inflammatory abnormalities in neuropsychological diseases.Front. Psychiatry2018942210.3389/fpsyt.2018.0042230245643
     [Google Scholar]
  83. RyanF.P. Human endogenous retroviruses in multiple sclerosis: Potential for novel neuro-pharmacological research.Curr. Neuropharmacol.20119236036910.2174/15701591179559656822131944
     [Google Scholar]
  84. GimenezJ. MalletF. ERVWE1 (endogenous retroviral family W, Env(C7), member 1).Atlas Genet. Cytogenet. Oncol. Haematol.2011210.4267/2042/38500
     [Google Scholar]
  85. CheynetV. RuggieriA. OriolG. BlondJ.L. BosonB. VachotL. VerrierB. CossetF.L. MalletF. Synthesis, assembly, and processing of the Env ERVWE1/syncytin human endogenous retroviral envelope.J. Virol.20057995585559310.1128/JVI.79.9.5585‑5593.200515827173
     [Google Scholar]
  86. RenardM. VarelaP.F. LetzelterC. DuquerroyS. ReyF.A. HeidmannT. Crystal structure of a pivotal domain of human syncytin-2, a 40 million years old endogenous retrovirus fusogenic envelope gene captured by primates.J. Mol. Biol.200535251029103410.1016/j.jmb.2005.07.05816140326
     [Google Scholar]
  87. GongR. PengX. KangS. FengH. HuangJ. ZhangW. LinD. TienP. XiaoG. Structural characterization of the fusion core in syncytin, envelope protein of human endogenous retrovirus family W.Biochem. Biophys. Res. Commun.200533141193120010.1016/j.bbrc.2005.04.03215883002
     [Google Scholar]
  88. EsnaultC. PrietS. RibetD. VernochetC. BrulsT. LavialleC. WeissenbachJ. HeidmannT. A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2.Proc. Natl. Acad. Sci. USA200810545175321753710.1073/pnas.080741310518988732
     [Google Scholar]
  89. BlondJ.L. LavilletteD. CheynetV. BoutonO. OriolG. Chapel-FernandesS. MandrandB. MalletF. CossetF.L. 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.20007473321332910.1128/JVI.74.7.3321‑3329.200010708449
     [Google Scholar]
  90. SapirA. AvinoamO. PodbilewiczB. ChernomordikL.V. Viral and developmental cell fusion mechanisms: conservation and divergence.Dev. Cell2008141112110.1016/j.devcel.2007.12.00818194649
     [Google Scholar]
  91. MangeneyM. RenardM. Schlecht-LoufG. BouallagaI. HeidmannO. LetzelterC. RichaudA. DucosB. HeidmannT. Placental syncytins: Genetic disjunction between the fusogenic and immunosuppressive activity of retroviral envelope proteins.Proc. Natl. Acad. Sci. USA200710451205342053910.1073/pnas.070787310518077339
     [Google Scholar]
  92. TolosaJ.M. SchjenkenJ.E. CliftonV.L. VargasA. BarbeauB. LowryP. MaitiK. SmithR. The endogenous retroviral envelope protein syncytin-1 inhibits LPS/PHA-stimulated cytokine responses in human blood and is sorted into placental exosomes.Placenta2012331193394110.1016/j.placenta.2012.08.00422999499
     [Google Scholar]
  93. LokossouA.G. ToudicC. NguyenP.T. ElisseeffX. VargasA. RassartÉ. LafondJ. LeducL. BourgaultS. GilbertC. ScorzaT. TolosaJ. BarbeauB. Endogenous retrovirus-encoded Syncytin-2 contributes to exosome-mediated immunosuppression of T cells†.Biol. Reprod.2019ioz12410.1093/biolre/ioz12431318021
     [Google Scholar]
  94. VargasA. ZhouS. Éthier-ChiassonM. FlipoD. LafondJ. GilbertC. BarbeauB. Syncytin proteins incorporated in placenta exosomes are important for cell uptake and show variation in abundance in serum exosomes from patients with preeclampsia.FASEB J.20142883703371910.1096/fj.13‑23905324812088
     [Google Scholar]
  95. UygurB. MelikovK. ArakelyanA. MargolisL.B. ChernomordikL.V. Syncytin 1 dependent horizontal transfer of marker genes from retrovirally transduced cells.Sci. Rep.2019911763710.1038/s41598‑019‑54178‑y31776415
     [Google Scholar]
  96. DePoloN.J. ReedJ.D. SheridanP.L. TownsendK. SauterS.L. JollyD.J. DubenskyT.W.Jr VSV-G pseudotyped lentiviral vector particles produced in human cells are inactivated by human serum.Mol. Ther.20002321822210.1006/mthe.2000.011610985952
     [Google Scholar]
  97. EricksonM. BanksW. Age-associated changes in the immune system and blood–brain barrier functions.Int. J. Mol. Sci.2019207163210.3390/ijms2007163230986918
     [Google Scholar]
  98. GrandiN. TramontanoE. Human endogenous retroviruses are ancient acquired elements still shaping innate immune responses.Front. Immunol.20189203910.3389/fimmu.2018.0203930250470
     [Google Scholar]
  99. ZhangH. MaH. YangX. FanL. TianS. NiuR. YanM. ZhengM. ZhangS. Cell fusion-related proteins and signaling pathways, and their roles in the development and progression of cancer.Front. Cell Dev. Biol.2022980966810.3389/fcell.2021.80966835178400
     [Google Scholar]
/content/journals/cgt/10.2174/0115665232303436240515071754
Loading
Human Virus-Like Proteins: Implications for Gene Therapy
Curr. Gene Ther. 25, 227 (2025); https://doi.org/10.2174/0115665232303436240515071754
/content/journals/cgt/10.2174/0115665232303436240515071754
/content/journals/cgt/10.2174/0115665232303436240515071754
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Arc/Arg3.1 protein; capsid; extracellular vesicle; gene therapy; Peg10; syncytin

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test