The carboxy-terminal p3Gag domain of the human foamy virus Gag precursor is required for efficient virus infectivity.
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 p74Gag derived from infected cells and/or purified virus particles. Using a recombinant HFV protease, we have determined the p74Gag cleavage site that results in p70Gag and the carboxy-terminal p3Gag (Pfrepper et al., 1997, Biochem. Biophys. Res. Commun. 237, 548-553). To study the biological functions of p3Gag, proviral DNA clones were constructed coding for a carboxy-terminally truncated p70Gag lacking the entire p3Gag protein. Removal of p3Gag 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 p74Gag protein in trans. The deletion of p3Gag resulted in particle assembly with wild-type virion morphology and encapsidation of Pol proteins. Our data show that the carboxy-terminal p3Gag 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.
Abteilung Retrovirale Genexpression, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
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Zemba
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Wilk
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Rutten
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Wagner
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Flügel
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Löchelt
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D006224:Cricetinae; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D015683:Gene Products, gag / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005814:Genes, Viral; D015750:Genes, gag; D006801:Humans; D008854:Microscopy, Electron; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D016092:Spumavirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D014774:Virulence
D017931:DNA Primers; D015683:Gene Products, gag; D011498:Protein Precursors