The C terminus of foamy retrovirus Gag contains determinants for encapsidation of Pol protein into virions.
Foamy viruses (FV) differ from orthoretroviruses in many aspects of their replication cycle. A major difference is in the mode of Pol expression, regulation, and encapsidation into virions. Orthoretroviruses synthesize Pol as a Gag-Pol fusion protein so that Pol is encapsidated into virus particles through Gag assembly domains. However, as FV express Pol independently of Gag from a spliced mRNA, packaging occurs through a distinct mechanism. FV genomic RNA contains cis-acting sequences that are required for Pol packaging, suggesting that Pol binds to RNA for its encapsidation. However, it is not known whether Gag is directly involved in Pol packaging. Previously our laboratory showed that sequences flanking the three glycine-arginine-rich (GR) boxes at the C terminus of FV Gag contain domains important for RNA packaging and Pol expression, cleavage, and packaging. We have now shown that both deletion and substitution mutations in the first GR box (GR1) prevented neither the assembly of particles with wild-type density nor packaging of RNA genomes but led to a defect in Pol packaging. Site-directed mutagenesis of GR1 indicated that the clustered positively charged amino acids in GR1 play important roles in Pol packaging. Our results suggest that GR1 contains a Pol interaction domain and that a Gag-Pol complex is formed and binds to RNA for incorporation into virions.
Lee
Eun-Gyung
EG
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Linial
Maxine L
ML
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D023061:Gene Order; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D015684:Gene Products, pol / Q000235:genetics / Q000378:metabolism*; D016679:Genome, Viral; D006801:Humans; D016297:Mutagenesis, Site-Directed; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D017384:Sequence Deletion; D016092:Spumavirus / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly
D015683:Gene Products, gag; D015684:Gene Products, pol; D014764:Viral Proteins