FIG. 6.

Model for the “intracellularization” of infectious retroviruses. A bona fide infectious retrovirus, e.g., the MusD progenitor, is endogenized upon infection of the germ line of a remote ancestor and Mendelian transmission to the following generations, thus resulting in a so-called ERV. This ERV may retain the characteristic features of retroviruses, i.e., produce infectious extracellular particles with a functional envelope protein, and be prone to horizontal transmission. Intracellularization is expected to correspond to an additional adaptation of the progenitor retrovirus, in which the produced VLPs are no longer able to exit or reenter the cell. For MusD, this has been achieved via the loss of the plasma membrane targeting function (degeneration of the myristoylation signal and basic domain at the N-terminal end of the matrix Gag protein) and the loss of the env gene. The resulting strictly intracellular life cycle resembles that of primitive Ty-like LTR-retrotransposons (although both classes of elements should be evolutionarily distinct) and is associated—at least in the case of the MusD element—with high-efficiency retrotransposition.