THE CARBOXY-TERMINAL P3(GAG) DOMAIN OF THE HUMAN FOAMY VIRUS GAG PRECURSOR IS REQUIRED FOR EFFICIENT VIRUS INFECTIVITY

Proteolytic processing of foamy virus Gag proteins appears to be diffe rent from that of other retroviruses. A single carboxy-terminal cleava ge site is consistently detectable in human foamy virus (HFV) Gag prec ursor protein p74(Gag) derived from infected cells and/or purified vir us particles. Using a recombinant HFV protease, we have determined the p74(Gag) cleavage site that results in p70(Gag) and the carboxy-termi nal 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 pr oteins 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-leng th p74(Gag) protein in trans. The deletion of p3(Gag) resulted in part icle assembly with wild-type virion morphology and encapsidation of Po l proteins. Our data show that the carboxy-terminal p3(Gag) protein ha s an important function for viral infectivity but is not required for preassembly of capsids, virus morphogenesis, and incorporation of Pol proteins into virions. (C) 1998 Academic Press.