Foamy virus Pol protein expressed as a Gag-Pol fusion retains enzymatic activities, allowing for infectious virus production.

Foamy viruses (FV) synthesize Pol from a spliced pol mRNA independently of Gag, unlike orthoretroviruses, which synthesize Pol as a Gag-Pol protein that coassembles with Gag. We found that prototype FV (PFV) mutants expressing Gag and Pol only as a Gag-Pol protein without the spliced Pol contain protease activity equivalent to that of wild-type (WT) Pol. Regardless of the presence or absence of the spliced Pol, the PFV Gag-Pol proteins can assemble into virus-like particles (VLPs), in contrast to the orthoretroviral Gag-Pol proteins, which cannot form VLPs. However, the PFV Gag-Pol VLPs have aberrant morphologies and are not infectious. In the absence of the spliced Pol, coexpression of a PFV Gag-Pol protein with Gag can produce infectious virions. Our results suggest that enzymes encoded by PFV pol (protease, reverse transcriptase, and integrase) are enzymatically active if they are synthesized as part of a Gag-Pol protein.