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Detection of respiratory syncytial virus fusion protein variants between 2009 and 2012 in China

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Abstract

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.

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Acknowledgements

We thank the staff at Department of Respiratory Medicine for assistance in collection of clinical specimens. We thank all the patients or individuals for their enrollment and participation for this study. This work was supported in part by a China Special Grant of the Prevention and Control of Infection Diseases [2009ZX10004-204] and a grant from the Second Colleges and Universities Excellent Talents Program in Chongqing (2011.1-2012.12).

Conflict of interest

The authors declared that there are no conflicts of interest.

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Authors and Affiliations

  1. Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing Medical University, Chongqing, 400014, China

    Qiuling Xia, Lili Zhou, Caijing Peng, Rui Hao, Ke Ni, Na Zang, Luo Ren & Lijia Wang

  2. Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, Chongqinq, 400014, China

    Yu Deng, Xiaohong Xie, Linli He, Daiyin Tian, Zhou Fu & Enmei Liu

  3. Chinese Ministry of Education Key Laboratory of Molecular Biology on Infectious Diseases, Chongqing Medical University, Chongqing, 400014, China

    Ailong Huang

  4. Department of Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Yao Zhao & Xiaodong Zhao

  5. Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong SRA, Pokfulam, China

    Wenwei Tu

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  1. Qiuling Xia
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Corresponding author

Correspondence to Enmei Liu.

Additional information

The GenBank accession numbers of the nucleotide sequences of complete RSV fusion protein genes obtained in this study are JX482018-JX482038 and JX682715-JX682823.

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Xia, Q., Zhou, L., Peng, C. et al. Detection of respiratory syncytial virus fusion protein variants between 2009 and 2012 in China. Arch Virol 159, 1089–1098 (2014). https://doi.org/10.1007/s00705-013-1870-9

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