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Retrovirology

, 6:P77 | Cite as

Emergence of intracellular genetic parasites from ancient retroviruses

  • David Ribet
  • Francis Harper
  • Marie Dewannieux
  • Gérard Pierron
  • Thierry Heidmann
Open Access
Poster presentation
  • 1.2k Downloads

Keywords

Viral Particle Gene Code Sequence Mendelian Fashion Intracellular Sequestration Genetic Parasite 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Background

Endogenous retroviruses are genetic parasites of mammalian genomes. They are « remnants » of ancestral infections by retroviruses that had integrated into the germ line of the host and were then transmitted vertically, in a Mendelian fashion. Studies of several endogenous retrovirus families have led to the identification of functional elements, able to replicate inside the host. Whereas some endogenous retroviruses behave as bona fide retroviruses, with a replicative cycle involving extracellular viral particles, some of them disclose a strictly intracellular amplification cycle with viral particles accumulating in the cytoplasm or in intracellular organelles.

Results

Throughout the study of two such ''intracellularized'' endogenous retroviruses, the murine MusD and IAP elements, we have deciphered the molecular events that have led to their emergence during evolution. We show that these elements derives from ancestral retroviruses by alteration of the plasma membrane targeting signal of the Gag protein, leading to the intracellular sequestration of the virus-like particles, followed by the decay of the env gene coding sequence. We demonstrate that replacement of the N-terminal Gag domain of MusD or IAP by that of infectious retroviruses restores the targeting of their viral particles to the plasma membrane and their release in the cell supernatant. These particles can further be pseudotyped with a functional Env protein and become infectious, thus reconstituting a bona fide functional retrovirus. Symmetrically, we were able to convert a ''classical'' endogenous retrovirus, named IAPE, into a functional ''intracellularized'' element by modifying its N-terminal Gag domain (Fig. 1A and 1B). This modified element gained the ability to efficiently amplify via a strictly intracellular cycle (Fig. 1C).
Figure 1

Conversion of a bona fide retrovirus to an ''intracellularized'' element. (A) Electronic microscopy images of viral particles produced by IAPE, a ''classical'' endogenous retrovirus, budding at the cell membrane. (B) Images of viral particles produced by a modified IAPE (in which the N-terminal domain of Gag was changed). Particles are accumulating in the endoplasmic reticulum after budding into the cisternae (inset). Pm, Plasma membrane; Nu, Nucleus; ERm, Endoplasmic reticulum membrane. (C) Intracellular amplification efficiency of IAPE and modified IAPE.

Conclusion

These results led us to propose a scenario that accounts for the generation, during evolution, of very successful intracellular genetic parasites from ancient retroviruses.

Copyright information

© Ribet et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

Authors and Affiliations

  • David Ribet
    • 1
    • 2
  • Francis Harper
    • 3
  • Marie Dewannieux
    • 1
    • 2
  • Gérard Pierron
    • 3
  • Thierry Heidmann
    • 1
    • 2
  1. 1.CNRS UMR 8122, Institut Gustave RoussyVillejuifFrance
  2. 2.Université Paris-SudOrsayFrance
  3. 3.FRE 2937, Institut André LwoffVillejuifFrance

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