Sequence variability of the respiratory syncytial virus (RSV) fusion gene among contemporary and historical genotypes of RSV/A and RSV/B.
Sequence variability of the respiratory syncytial virus (RSV) fusion gene among contemporary and historical genotypes of RSV/A and RSV/B.
复制标题
DOI：
10.1371/journal.pone.0175792
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Piedra PA
中科院分区：
文献类型：
--
作者：
Hause AM;Henke DM;Avadhanula V;Shaw CA;Tapia LI;Piedra PA
RSV的融合(F)蛋白是主要的疫苗靶点。这种蛋白质经历了从融合前到融合后的构象变化。两种构象具有相同的抗原位点II和IV。预融合F具有独特的抗原位点p27、ø、α2α3β3β4和MPE8；然而，融合后的F具有独特的抗原位点i。我们的目的是确定RSV/A和RSV/B分离株与历史RSV/A菌株相比，来自当代和历史基因型的抗原变异性。F序列来自GenBank、休斯顿和智利（N = 1,090）的分离株。将序列与历史RSV/ a Long菌株的参考序列进行配对比较。变异（以%计算）定义为与参考序列相比，每个氨基酸（aa）位置的变化。只有抗原位点变异率≥5%的aa被报道。共分析1090个序列，其中RSV/A 822个，RSV/B 268个。与参考文献F相比，非同义变化最多的结构域包括信号肽、p27、七肽重复结构域2、抗原位点ø和跨膜结构域。RSV/A亚组抗原位点有7aa的变化，分别为I位点（N = 1）、II位点（N = 1）、p27位点（N = 4）、α2α3β3β4（AM14）位点（N = 1），频率为7 ~ 91%。相比而言，RSV/B在抗原位点I （N = 3）、II （N = 1）、p27 （N = 9）、ø （N = 4）、α2α3β3β4(AM14) （N = 1）和MPE8 （N = 1）上发生了19个aa的变化，频率在79% ~ 100%之间。虽然RSV F的抗原位点通常保守得很好，但将这两个亚群与参考RSV/A Long菌株进行比较时发现差异。此外，这些差异在RSV/B分离株融合前F的抗原位点上更为突出，经常以100%的频率出现。如果RSV/ a历史GA1基因型的单价F蛋白用于疫苗开发，这可能是重要的。
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.