The Carboxy-Terminal p3GagDomain of the Human Foamy Virus Gag Precursor Is Required for Efficient Virus Infectivity

Abstract Proteolytic processing of foamy virus Gag proteins appears to be different from that of other retroviruses. A single carboxy-terminal cleavage site is consistently detectable in human foamy virus (HFV) Gag precursor protein p74 Gag derived from infected cells and/or purified virus particles. Using a recombinant HFV protease, we have determined the p74 Gag cleavage site that results in p70 Gag and the carboxy-terminal p3 Gag (Pfrepper et al., 1997, Biochem. Biophys. Res. Commun. 237, 548–553). To study the biological functions of p3 Gag , proviral DNA clones were constructed coding for a carboxy-terminally truncated p70 Gag lacking the entire p3 Gag protein. Removal of p3 Gag resulted in an about 100-fold lower virus titer. The expression of other HFV proteins and the processing of Pol proteins were indistinguishable from those of wild-type-transfected cells. The defect in viral infectivity of the p3 mutants was partially restored by coexpressing the full-length p74 Gag protein in trans. The deletion of p3 Gag resulted in particle assembly with wild-type virion morphology and encapsidation of Pol proteins. Our data show that the carboxy-terminal p3 Gag protein has an important function for viral infectivity but is not required for preassembly of capsids, virus morphogenesis, and incorporation of Pol proteins into virions.