From Viruses to Genes: Syncytins

  • Philippe Pérot
  • Pierre-Adrien Bolze
  • François MalletEmail author


The content of 5–90 million years old retroviruses and even older retrotransposons of animal genomes and the wide variety of modern retroviruses infecting the same range of species suggest that these elements can be assimilated to shuttle across evolution. A snapshot taken a few decades ago showed us the capture of cellular proto-oncogenes by infectious elements, representing the dark side of the communication between the worlds of viruses and animals. Another snapshot we took more recently shows multiple captures by animal genomes of envelope genes originating from infectious retroviruses, illustrating a phenomenon of convergent evolution. This could be seen as the bright side of these relations as those envelopes were shown to be involved in the earlier steps of human development, i.e. fusion of placental syncytiotrophoblastic layer, therefore they were dubbed Syncytins. Sequencing of more and more animal genomes allowed comparative genomic analyses that revealed how these envelopes have been domesticated in human, mouse, goat, rabbit, etc. More generally, we illustrate in this chapter how close are the viral and animal genome worlds and, focusing mainly on the hominoid ERVWE1 locus encoding Synctin-1, how the different proviruses encoding Syncytins have been domesticated to achieve placental functions. Influence of the chromosomal integration context, the epigenetic control and the splicing strategy upon transcription, and protein maturation processes as well will be discussed in order to illustrate what makes these nowadays genes different from their ancestral infectious counterpart. The price to pay for this beneficial invasion will be illustrated by the possible implications of Syncytin-1 in a wide range of diseases. Last, the apparent stringency of placental regulation will await to be challenged as regard to the evidence of expression in other physiological fusogenic contexts such as myoblasts and osteoclasts.


Retrovirus Endogenous retrovirus Syncytins Domestication 



Avian leukosis virus


Baboon endogenous virus


Bovine leukemia virus


Cytoplasmic tail




Endometrial carcinoma




Endoplasmic reticulum


Endogenous retrovirus




Felis catus endogenous retrovirus


Fusion peptide


Glial cell missing






Hemolysis, elevated liver enzymes and low platelets


Human endogenous retrovirus


Human foamy virus


Human immunodeficiency virus


Human T-cell leukemia virus


Jaagsiekte sheep retrovirus


Koala retrovirus


Long terminal repeat




Mammalian apparent LTR-retrotransposon


Morpholino antisense oligonucleotide


Murine leukemia virus


Mouse mammary tumor virus


Mason-Pfizer monkey virus


Multiple sclerosis


Multiple sclerosis associated retrovirus


Nitric oxide


Old astrocytes specifically induced substance


Open reading frame


Peripheral blood mononuclear cell


Primer binding site


Polymerase chain reaction


Papio cynocephalus retrovirus




Receptor-binding domain


A feline endogenous retrovirus


Reverse transcriptase


Simian endogenous retrovirus


Simian immunodeficiency virus


Spleen Necrosis virus


Signal peptide


Simian retrovirus


Surface unit


Transmembrane unit


Transmembrane domain


Upstream regulatory element


Walleye dermal sarcoma



We thank Danièle Evain-Brion, Thierry Heidmann, Thomas E. Spencer, and François-Loïc Cosset for providing pictures and photographs. We are grateful to Laurent Duret for his support in bioinformatics, and we want to pay a tribute to Jean de La Fontaine for the contribution that his fable on the domestication ‘The Wolf and the Dog’ brought to our scientific reflection.

Dedicate On behalf of past and present members of the Mallet’s group, we would like to dedicate this chapter to the memory of our colleague and friend Olivier Bouton who substantially contributed to the human and scientific adventure that was the MSRV/HERV-W/ERVWE1 discovery.


Advanced Diagnostics for New Therapeutic Approaches (ADNA), a program dedicated to personalized Medicine, coordinated by Mérieux Alliance and supported by the French public agency, OSEO. PP and FM are employees of bioMérieux SA. PAB was supported by a grant from the Ministère français du Travail, de l’Emploi et de la Santé.


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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Philippe Pérot
    • 1
  • Pierre-Adrien Bolze
    • 1
    • 2
  • François Mallet
    • 1
    Email author
  1. 1.Cancer Biomarkers Research Group, Centre Hospitalier Lyon SudLaboratoire Commun de Recherche Hospices Civils de Lyon – bioMérieuxPierre-Bénite CedexFrance
  2. 2.Hospices Civils de Lyon, Centre Hospitalier Universitaire Lyon Sud, Centre de Référence des Maladies TrophoblastiquesUniversité Claude Bernard Lyon 1Pierre-Bénite CedexFrance

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