Mutations of respiratory syncytial virus attachment glycoprotein G associated with resistance to neutralization by primate polyclonal antibodies.
The respiratory syncytial (RS) virus attachment glycoprotein G is a type II transmembrane glycoprotein and an important target of the host immune response. Antigenic variability of the G protein is postulated to contribute to the ability of the virus to evade established immune responses. A glycoprotein G monospecific polyclonal antiserum from a nonhuman primate was used to select for an antibody resistant RS virus. The mutant virus was resistant to neutralization by the selecting antiserum and by the sera from three other G-protein immunized primates. G-protein amino acid changes were found at residues 61 (Phe to Leu), 174 (Ser to Cys), and 183 (Trp to Leu). Thus the mutant protein had amino acid changes in the transmembrane domain (61) and the central ectodomain (174 and 183). The change at amino acid 174 resulted in five rather than the usual four Cys found in the conserved central region of the ectodomain. These data demonstrate that an RS virus with resistance to neutralization by polyclonal antibodies can be selected readily in cell culture. In addition, only a limited number of amino acid changes is required to produce the resistant phenotype.
Sullender
W M
WM
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA. Pedp019@uabdpo.dpo.uab.edu
Edwards
K G
KG
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral / Q000276:immunology*; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D002522:Chlorocebus aethiops; D015707:HN Protein; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011323:Primates; D012136:Respiratory Syncytial Viruses / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000235:genetics* / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D015707:HN Protein; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G