Sequence variability of the respiratory syncytial virus (RSV) fusion gene among contemporary and historical genotypes of RSV/A and RSV/B

The fusion (F) protein of RSV is the major vaccine target. This protein undergoes a conformational change from pre-fusion to post-fusion. Both conformations share antigenic sites II and IV. Pre-fusion F has unique antigenic sites p27, ø, α2α3β3β4, and MPE8; whereas, post-fusion F has unique antigeni...

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Bibliographic Details
Published in:PloS one 2017-04, Vol.12 (4), p.e0175792-e0175792
Main Authors: Hause, Anne M, Henke, David M, Avadhanula, Vasanthi, Shaw, Chad A, Tapia, Lorena I, Piedra, Pedro A
Format: Article
Language:English
Subjects:
Acids
Age
Amino Acid Sequence
Amino Acid Substitution
Analysis
Antibodies
Antibodies, Viral - blood
Antibody response
Antigenic Variation
Antigens
Antigens, Viral - chemistry
Antigens, Viral - genetics
Attachment
Biology and Life Sciences
Children
Circulation
Communities
Computer and Information Sciences
Data acquisition
Data collection
Data processing
Decision analysis
Electronic publishing
Epidemics
Epidemiology
Epitope mapping
F gene
F protein
Fusion protein
Gene mapping
Genes
Genes, Viral
Genetic aspects
Genetic diversity
Genetic Variation
Genetics
Genotype
Genotype & phenotype
Genotypes
Glycoproteins
Humans
Immunization
Infants
Inhibitors
Intervention
Libraries
Medicine
Medicine and Health Sciences
Microbiology
Nucleotides
Pediatrics
Phylogeny
Physical Sciences
Protein Conformation
Protein structure
Proteins
Reproduction (copying)
Research and Analysis Methods
Respiratory syncytial virus
Respiratory Syncytial Virus Infections - immunology
Respiratory Syncytial Virus Infections - prevention & control
Respiratory Syncytial Virus Infections - virology
Respiratory Syncytial Virus Vaccines - genetics
Respiratory Syncytial Virus Vaccines - immunology
Respiratory Syncytial Virus, Human - classification
Respiratory Syncytial Virus, Human - genetics
Respiratory Syncytial Virus, Human - immunology
Respiratory tract
Science
Seasons
Stellar mass
Surgery
Vaccine development
Vaccines
Variability
Viral Fusion Proteins - chemistry
Viral Fusion Proteins - genetics
Viral Fusion Proteins - immunology
Virology
Viruses
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Summary:The fusion (F) protein of RSV is the major vaccine target. This protein undergoes a conformational change from pre-fusion to post-fusion. Both conformations share antigenic sites II and IV. Pre-fusion F has unique antigenic sites p27, ø, α2α3β3β4, and MPE8; whereas, post-fusion F has unique antigenic site I. Our objective was to determine the antigenic variability for RSV/A and RSV/B isolates from contemporary and historical genotypes compared to a historical RSV/A strain. The F sequences of isolates from GenBank, Houston, and Chile (N = 1,090) were used for this analysis. Sequences were compared pair-wise to a reference sequence, a historical RSV/A Long strain. Variability (calculated as %) was defined as changes at each amino acid (aa) position when compared to the reference sequence. Only aa at antigenic sites with variability ≥5% were reported. A total of 1,090 sequences (822 RSV/A and 268 RSV/B) were analyzed. When compared to the reference F, those domains with the greatest number of non-synonymous changes included the signal peptide, p27, heptad repeat domain 2, antigenic site ø, and the transmembrane domain. RSV/A subgroup had 7 aa changes in the antigenic sites: site I (N = 1), II (N = 1), p27 (N = 4), α2α3β3β4(AM14) (N = 1), ranging in frequency from 7-91%. In comparison, RSV/B had 19 aa changes in antigenic sites: I (N = 3), II (N = 1), p27 (N = 9), ø (N = 4), α2α3β3β4(AM14) (N = 1), and MPE8 (N = 1), ranging in frequency from 79-100%. Although antigenic sites of RSV F are generally well conserved, differences are observed when comparing the two subgroups to the reference RSV/A Long strain. Further, these discrepancies are accented in the antigenic sites in pre-fusion F of RSV/B isolates, often occurring with a frequency of 100%. This could be of importance if a monovalent F protein from the historical GA1 genotype of RSV/A is used for vaccine development.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0175792