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From Viruses to Genes: Syncytins

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

Abstract

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.

Keywords

Retrovirus Endogenous retrovirus Syncytins Domestication 

Abbreviations

ALV

Avian leukosis virus

BaEV

Baboon endogenous virus

BLV

Bovine leukemia virus

cyt

Cytoplasmic tail

en

Endogenous

EnCa

Endometrial carcinoma

Env

Envelope

ER

Endoplasmic reticulum

ERV

Endogenous retrovirus

Exo

Exogenous

FcEV

Felis catus endogenous retrovirus

FP

Fusion peptide

GCM

Glial cell missing

GPI

Glycosylphosphatidylinositol

h

Human

HELLP

Hemolysis, elevated liver enzymes and low platelets

HERV

Human endogenous retrovirus

HFV

Human foamy virus

HIV

Human immunodeficiency virus

HTLV

Human T-cell leukemia virus

JSRV

Jaagsiekte sheep retrovirus

KoRV

Koala retrovirus

LTR

Long terminal repeat

m

Mouse

MALR

Mammalian apparent LTR-retrotransposon

MAO

Morpholino antisense oligonucleotide

MLV

Murine leukemia virus

MMTV

Mouse mammary tumor virus

MPMV

Mason-Pfizer monkey virus

MS

Multiple sclerosis

MSRV

Multiple sclerosis associated retrovirus

NO

Nitric oxide

OASIS

Old astrocytes specifically induced substance

ORF

Open reading frame

PBMC

Peripheral blood mononuclear cell

PBS

Primer binding site

PCR

Polymerase chain reaction

PcRV

Papio cynocephalus retrovirus

PE

Preeclampsia

RBD

Receptor-binding domain

RD114

A feline endogenous retrovirus

RT

Reverse transcriptase

SERV

Simian endogenous retrovirus

SIV

Simian immunodeficiency virus

SNV

Spleen Necrosis virus

SP

Signal peptide

SRV

Simian retrovirus

SU

Surface unit

TM

Transmembrane unit

tm

Transmembrane domain

URE

Upstream regulatory element

WDS

Walleye dermal sarcoma

Notes

Acknowledgements

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.

Funding

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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