title: A model for the generation of multiple A to G transitions in the human respiratory syncytial virus genome: predicted RNA secondary structures as substrates for adenosine deaminases that act on RNA.
abstract: Human respiratory syncytial virus (HRSV) escape mutants selected with antibodies specific for the attachment (G) protein contain diverse genetic alterations, including point mutations, premature stop codons, frame shift changes and A to G hypermutations. The latter changes have only been found in mutants selected with antibodies directed against the conserved central region of the G protein. This gene segment fulfils substrate requirements for adenosine deaminases that act on RNA (ADARs): i.e. it is an A+U rich region of 137 residues, and 98 or 106 of them--for A/Mon/3/88 or Long HRSV strains, respectively--are predicted to form intramolecular base pairs leading to a stable RNA secondary structure. In addition, when sequences of the G gene from natural isolates are compared in terms of pairwise substitutions, A to G+G to A changes are preferentially observed in regions where stable intramolecular dsRNA secondary structures are predicted to occur. In this study, a model is proposed in which, in addition to nucleotide misincorporations, reiterative A to G changes in HRSV are generated by ADAR activity operating in short segments (100-200 ribonucleotide residues) of the HRSV genome with high tendency for intramolecular base pairing.
authors.affiliation: Centro Nacional de Biología Fundamental, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain1.
authors.forename: Isidoro
authors.initials: I
authors.lastname: Martínez
authors.affiliation: Centro Nacional de Biología Fundamental, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain1.
authors.forename: José A
authors.initials: JA
authors.lastname: Melero
mesh_terms: D000225:Adenine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D001483:Base Sequence; D016679:Genome, Viral; D006147:Guanine; D015707:HN Protein / Q000235:genetics / Q000276:immunology; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism*; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics*; D014759:Viral Envelope Proteins
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015707:HN Protein; D012367:RNA, Viral; D014759:Viral Envelope Proteins; C116204:attachment protein G; D006147:Guanine; D000243:Adenosine Deaminase; D000225:Adenine