Detection of respiratory syncytial virus fusion protein variants between 2009 and 2012 in China
Detection of respiratory syncytial virus fusion protein variants between 2009 and 2012 in China
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DOI：
10.1007/s00705-013-1870-9
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发表时间：
2014-05-01
影响因子：
2.7
通讯作者：
Liu, Enmei
中科院分区：
文献类型：
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作者：
Xia, Qiuling;Zhou, Lili;Liu, Enmei
呼吸道合胞病毒（RSV）在儿童早期引起呼吸道感染，特别是急性下呼吸道感染（ALRTI）。RSV融合蛋白（F蛋白）是重要的表面蛋白，并且它是细胞毒性T淋巴细胞（CTL）和中和抗体的靶;因此，它可用作疫苗研究的候选物。本研究调查了RSV F蛋白的遗传多样性。为此，在2009年6月至2012年3月期间，共收集了1800例ALRTI住院儿童的鼻咽抽吸物进行病毒分离。RSV阳性333例（A型277例，B型55例，A、B型各1例），占18.5%。然后，选择130个临床株（RSV A 107个，RSV B 23个）进行F基因测序。系统发育分析表明，F基因序列高度保守，在残基16、25、45、102、122、124、209和447处具有显著的氨基酸变化。还观察到人类组织相容性白细胞抗原（HLA）限制性CTL表位的突变。在帕利珠单抗结合位点276（N -> S）处的RSV A F蛋白的变异在2009年至2012年之间增加并成为主导。蛋白质印迹分析和微量中和数据显示RSV A中残基276（N -> S）处的取代，其不引起对帕利珠单抗的抗性。总之，RSV F基因在地理上和时间上是保守的，但仍观察到有限的遗传变异。这些数据可能有助于开发针对RSV感染的疫苗。
Respiratory syncytial virus (RSV) causes respiratory tract infection, particularly acute lower respiratory tract infection (ALRTI), in early childhood. The RSV fusion protein (F protein) is an important surface protein, and it is the target of both cytotoxic T lymphocytes (CTL) and neutralizing antibodies; thus, it may be useful as a candidate for vaccine research. This study investigated the genetic diversity of the RSV F protein. To this end, a total of 1800 nasopharyngeal aspirates from hospitalized children with ALRTI were collected for virus isolation between June 2009 and March 2012. There were 333 RSV-positive cases (277 cases of RSV A, 55 of RSV B, and 1 with both RSV A and RSV B), accounting for 18.5 % of the total cases. Next, 130 clinical strains (107 of RSV A, 23 of RSV B) were selected for F gene sequencing. Phylogenetic analysis revealed that the F gene sequence is highly conserved, with significant amino acid changes at residues 16, 25, 45, 102, 122, 124, 209, and 447. Mutations in human histocompatibility leukocyte antigen (HLA)-restricted CTL epitopes were also observed. Variations in RSV A F protein at the palivizumab binding site 276 (N -> S) increased between 2009 and 2012 and became predominant. Western blot analysis and microneutralization data showed a substitution at residue 276 (N -> S) in RSV A that did not cause resistance to palivizumab. In conclusion, the RSV F gene is geographically and temporally conserved, but limited genetic variations were still observed. These data could be helpful for the development of vaccines against RSV infection.