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. 2017 Apr 17;12(4):e0175792.
doi: 10.1371/journal.pone.0175792. eCollection 2017.

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

Anne M Hause  1   2 , David M Henke  3 , Vasanthi Avadhanula  1 , Chad A Shaw  3 , Lorena I Tapia  4   5 , Pedro A Piedra  1   6
Affiliations

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

Anne M Hause et al. PLoS One. .

Erratum in

Abstract

Background: 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.

Methods: 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.

Results: 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%.

Discussion: 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Appearance of RSV/A and RSV/B genotypes and dominance over time (1961–2014).
Sequences assigned genotypes were assessed by their sample acquisition date. The included inset depicts those years (1961–2000) with a small number of available sequences.
Fig 2
Fig 2. The fusion genes of RSV/A isolates are more similar to the RSV/A Long strain than RSV/B isolates.
Non-synonymous/synonymous ratio graph of amino acids with non-synonymous or synonomous changes in the fusion gene for a) RSV/A isolates and b) RSV/B isolates (compared to the RSV/A Long strain). Fusion gene domains are depicted by assigned color blocks. Antigenic sites are highlighted in shades of gray respective to the protein conformation on which they are found.
Fig 3
Fig 3. The entropy values in amino acids within antigenic sites of the fusion gene of RSV/A and RSV/B have a similar distribution.
Entropy was defined as ∑i−i log(i). Individual genotypes of each subgroup contributed equally to the proportion of amino acids found at a given residue.
See this image and copyright information in PMC

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