RT Journal Article T1 Conservation of G-Protein Epitopes in Respiratory Syncytial Virus (Group A) despite Broad Genetic Diversity: Is Antibody Selection Involved in Virus Evolution? A1 Trento, Alfonsina A1 Ábrego, Leyda A1 Rodríguez Fernández, Rosa María A1 l González-Sánchez, María Isabel A1 González-Martínez, Felipe A1 Delfraro, Adriana A1 Pascale, Juan M. A1 Arbiza, Juan A1 Melero, José A. AB Worldwide G-glycoprotein phylogeny of human respiratory syncytial virus (hRSV) group A sequences revealed diversification in major clades and genotypes over more than 50 years of recorded history. Multiple genotypes cocirculated during prolonged periods of time, but recent dominance of the GA2 genotype was noticed in several studies, and it is highlighted here with sequences from viruses circulating recently in Spain and Panama. Reactivity of group A viruses with monoclonal antibodies (MAbs) that recognize strain-variable epitopes of the G glycoprotein failed to correlate genotype diversification with antibody reactivity. Additionally, no clear correlation was found between changes in strain-variable epitopes and predicted sites of positive selection, despite both traits being associated with the C-terminal third of the G glycoprotein. Hence, our data do not lend support to the proposed antibody-driven selection of variants as a major determinant of hRSV evolution. Other alternative mechanisms are considered to account for the high degree of hRSV G-protein variability PB jvi.asm.org YR 2015 FD 2015-02-20 LK https://hdl.handle.net/20.500.14352/117257 UL https://hdl.handle.net/20.500.14352/117257 LA eng NO Trento A, Ábrego L, Rodriguez-Fernandez R, González-Sánchez MI, González-Martínez F, Delfraro A, Pascale JM, Arbiza J, Melero JA. Conservation of G-Protein Epitopes in Respiratory Syncytial Virus (Group A) Despite Broad Genetic Diversity: Is Antibody Selection Involved in Virus Evolution? J Virol. 2015 Aug;89(15):7776-85. doi: 10.1128/JVI.00467-15. Epub 2015 May 20. PMID: 25995258; PMCID: PMC4505632. NO Importance: An unusual characteristic of the G glycoprotein of human respiratory syncytial virus (hRSV) is the accumulation of nonsynonymous (N) changes at higher rates than synonymous (S) changes, reaching dN/dS values at certain sites predictive of positive selection. Since these sites cluster preferentially in the C-terminal third of the G protein, like certain epitopes recognized by murine antibodies, it was proposed that immune (antibody) selection might be driving the apparent positive selection, analogous to the antigenic drift observed in the influenza virus hemagglutinin (HA). However, careful antigenic and genetic comparison of the G glycoprotein does not provide evidence of antigenic drift in the G molecule, in agreement with recently published data which did not indicate antigenic drift in the G protein with human sera. Alternative explanations to the immune-driven selection hypothesis are offered to account for the high level of G-protein genetic diversity highlighted in this study DS Docta Complutense RD 6 abr 2025