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The mouse IAPE endogenous retrovirus can infect cells through any of the five GPI-anchored Ephrin A proteins.

By Marie Dewannieux, Cécile Vernochet, David Ribet, Birke Bartosch, François-Loïc Cosset and Thierry Heidmann

Abstract

International audienceThe IAPE (Intracisternal A-type Particles elements with an Envelope) family of murine endogenous retroelements is present at more than 200 copies in the mouse genome. We had previously identified a single copy that proved to be fully functional, i.e. which can generate viral particles budding out of the cell and infectious on a series of cells, including human cells. We also showed that IAPE are the progenitors of the highly reiterated IAP elements. The latter are now strictly intracellular retrotransposons, due to the loss of the envelope gene and re-localisation of the associated particles in the course of evolution. In the present study we searched for the cellular receptor of the IAPE elements, by using a lentiviral human cDNA library and a pseudotype assay on transduced cells. We identified Ephrin A4, a GPI-anchored molecule involved in several developmental processes, as a receptor for the IAPE pseudotypes. We also found that the other 4 members of the Ephrin A family -but not those of the closely related Ephrin B family- were also able to mediate IAPE cell entry, thus significantly increasing the amount of possible cell types susceptible to IAPE infection. We show that these include mouse germline cells, as illustrated by immunohistochemistry experiments, consistent with IAPE genomic amplification by successive re-infection. We propose that the uncovered properties of the identified receptors played a role in the accumulation of IAPE elements in the mouse genome, and in the survival of a functional copy

Topics: MESH : Animals, MESH : Cercopithecus aethiops, MESH : HEK293 Cells, MESH : Host-Pathogen Interactions, MESH : Humans, MESH : Mice, MESH : Ovary, MESH : Retroviridae Infections, MESH : Vero Cells, MESH : Virus Replication, MESH : Endogenous Retroviruses, MESH : Ephrin-A4, MESH : Ephrins, MESH : Female, MESH : Gene Expression Regulation, Viral, MESH : Gene Library, MESH : Genes, Intracisternal A-Particle, MESH : Genes, Viral, [ SDV.CAN ] Life Sciences [q-bio]/Cancer
Publisher: Public Library of Science
Year: 2011
DOI identifier: 10.1371/journal.ppat.1002309
OAI identifier: oai:HAL:hal-00795018v1
Provided by: Hal-Diderot
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