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Increased susceptibility of human respiratory syncytial virus to neutralization by anti-fusion protein antibodies on adaptation to replication in cell culture.

Abstract：

:Subgroup A respiratory syncytial viruses present in respiratory secretions and low passage level cell culture isolates were found to be markedly less susceptible to neutralization with monoclonal antibodies (MAbs) to the F glycoprotein than the cell culture adapted A2 virus strain. Low passage virus isolates collected over a 20 year period and belonging to several sub-group A lineages were refractory to neutralization with antibodies recognizing two major neutralizing antigenic sites located sub-terminally at opposite ends of the F(1) glycoprotein sub-unit. On further passage in cell culture, virus isolates exhibited both increased infectivity titers and increased susceptibility to neutralization by antibodies to both antigenic sites. The consensus nucleotide sequence of the membrane associated proteins M and of the SH, G and F glycoprotein genes, and their intergenic regions were compared for neutralization resistant and susceptible stocks of one virus strain, R17532. No changes were observed in the known monoclonal antibody epitopes on the F glycoprotein. In line with this, the increase in susceptibility was not found to be associated with any increased binding of monoclonal antibody to isolated F glycoprotein in a BIAcore assay, thus excluding the possibility that passage in cell culture selected for viruses with mutations in the antibody binding sites. M and SH genes were conserved but a number of sites in the G and F glycoprotein genes were found to vary on adaptation to cell culture suggesting that change in susceptibility to neutralization was associated with a change in the prevalent quasispecies present in the virus population. The genetic basis of phenotypic change in susceptibility remains to be determined.

journal_name

J Med Virol

journal_title

Journal of medical virology

authors

Marsh R,Connor A,Gias E,Toms GL

doi

10.1002/jmv.20892

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

829-37

issue

eissn

0146-6615

issn

1096-9071

journal_volume

pub_type

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Increased susceptibility of human respiratory syncytial virus to neutralization by anti-fusion protein antibodies on adaptation to replication in cell culture.