Abstract
The 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.
Highlights
Mammalian genomes are filled with numerous copies of mobile genetic elements
The mouse IAPE family is interesting in this respect: we previously demonstrated that it is the progenitor of the intracellular IAP elements [10], which are probably the most successful and active family of retrotransposons in the mouse, being responsible for an estimated 10% of the de novo mutations occurring in laboratory animals
Some of them, called endogenous retroviruses, have a structure similar to that observed for the integrated form of infectious retroviruses
Summary
Mammalian genomes are filled with numerous copies of mobile genetic elements. Among them, endogenous retroviruses are the remnants of infectious retroviruses that once infected the germline of their host and have since been transmitted from one generation to the other following a mendelian pattern (reviewed in refs. [1,2,3]). The most successful families of elements (with regards to their copy number) identified so far have switched to a strictly intracellular amplification mechanism that does not require the viral particles to be exposed to the extracellular compartment and that makes them much more efficient (reviewed in [9,10]) This switch in the amplification strategy is usually correlated to the loss of the envelope (env) gene that encodes the membrane glycoprotein responsible for the binding of the particle to a cellular protein used as a receptor, and a modification of the intracellular trafficking of the particles via an alteration of the N-terminal part of the structural Gag protein.
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