Foamy virus reverse transcriptase is expressed independently from the Gag protein.
In the foamy virus (FV) subgroup of retroviruses the pol genes are located in the +1 reading frame relative to the gag genes and possess potential ATG initiation codons in their 5' regions. This genome organization suggests either a + 1 ribosomal frameshift to generate a Gag-Pol fusion protein, similar to all other retroviruses studied so far, or new initiation of Pol translation, as used by pararetroviruses, to express the Pol protein. By using a genetic approach we have ruled out the former possibility and provide evidence for the latter. Two down-mutations (M53 and M54) of the pol ATG codon were found to abolish replication and Pol protein expression of the human FV isolate. The introduction of a new ATG in mutation M55, 3' to the down-mutated ATG of mutation M53, restored replication competence, indicating that the pol ATG functions as a translational initiation codon. Two nonsense mutants (M56 and M57), which functionally separated gag and pol with respect to potential frame-shifting sites, were also replication-competent, providing further genetic evidence that FVs express the Pol protein independently from Gag. Our results show that during a particular step of the replication cycle, FVs differ fundamentally from all other retroviruses.
Enssle
J
J
Institut für Virologie und Immunbiologie, Würzburg, Germany.
Jordan
I
I
Mauer
B
B
Rethwilm
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D016368:Frameshift Mutation; D015683:Gene Products, gag / Q000096:biosynthesis*; D015684:Gene Products, pol / Q000096:biosynthesis; D015750:Genes, gag; D015751:Genes, pol; D016679:Genome, Viral; D006801:Humans; D007668:Kidney; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010442:Peptide Chain Initiation, Translational; D014176:Protein Biosynthesis; D012194:RNA-Directed DNA Polymerase / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012270:Ribosomes / Q000378:metabolism; D016092:Spumavirus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D014779:Virus Replication
D015683:Gene Products, gag; D015684:Gene Products, pol; D011993:Recombinant Fusion Proteins; D012194:RNA-Directed DNA Polymerase