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. and ). This modified element gained the ability to efficiently amplify via a strictly intracellular cycle (Fig. ).
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 (more ...)