Abstract
Background
Previous serological studies of human bocavirus (HBoV) 1 could not exclude cross-reactivity with the other three HBoVs, particularly HBoV2.
Methods
To search for genotype-specific antibodies against HBoV1 and HBoV2, the divergent regions (DRs) located on the major capsid protein VP3 were defined through viral amino acid alignment and structure prediction. DR-deduced peptides were used as antigens to harvest corresponding anti-DR rabbit sera. To determine their genotype specificities for HBoV1 and HBoV2, these sera samples were used as antibodies against the antigens VP3 of HBoV1 and HBoV2 (expressed in Escherichia coli) in western blotting (WB), enzyme-linked immunosorbent assay (ELISA), and bio-layer interferometry (BLI) assays. Subsequently, the antibodies were evaluated with clinical specimens from pediatric patients with acute respiratory tract infection by indirect immunofluorescence assay (IFA).
Results
There were four DRs (DR1–4) located on VP3 with different secondary and tertiary structures between HBoV1 and HBoV2. Regarding the reactivity with VP3 of HBoV1 or HBoV2 in WB and ELISA, high intra-genotype cross-reactivity of anti-HBoV1 or HBoV2 DR1, DR3, and DR4, but not anti-DR2, was observed. Genotype-specific binding capacity of anti-DR2 sera was confirmed by BLI and IFA, in which only anti-HBoV1 DR2 antibody reacted with HBoV1-positive respiratory specimens.
Conclusion
Antibodies against DR2, located on VP3 of HBoV1 or HBoV2, were genotype specific for HBoV1 and HBoV2, respectively.
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Data availability
Data will be made available on reasonable request.
References
Allander T, Tammi MT, Eriksson M, Bjerkner A, Tiveljung-Lindell A, Andersson B. Cloning of a human parvovirus by molecular screening of respiratory tract samples. Proc Natl Acad Sci U S A. 2005;102:12891–6.
Kapoor A, Slikas E, Simmonds P, Chieochansin T, Naeem A, Shaukat S, et al. A newly identified bocavirus species in human stool. J Infect Dis. 2009;199:196–200.
Kapoor A, Simmonds P, Slikas E, Li L, Bodhidatta L, Sethabutr O, et al. Human bocaviruses are highly diverse, dispersed, recombination prone, and prevalent in enteric infections. J Infect Dis. 2010;201:1633–43.
Zhao M, Zhu R, Qian Y, Deng J, Wang F, Sun Y, et al. Prevalence and phylogenetic analysis of human bocaviruses 1–4 in pediatric patients with various infectious diseases. PLoS One. 2016;11:e0160603.
Kumthip K, Khamrin P, Ushijima H, Maneekarn N. The predominance of human bocavirus genotypes 1 and 2 in oysters in Thailand. Appl Environ Microbiol. 2021;87:e0045621.
Qiu J, Söderlund-Venermo M, Young NS. Human parvoviruses. Clin Microbiol Rev. 2017;30:43–113.
Söderlund-Venermo M. Emerging human parvoviruses: the rocky road to fame. Annu Rev Virol. 2019;6:71–91.
Chieochansin T, Kapoor A, Delwart E, Poovorawan Y, Simmonds P. Absence of detectable replication of human bocavirus species 2 in respiratory tract. Emerg Infect Dis. 2009;15:1503–5.
Arthur JL, Higgins GD, Davidson GP, Givney RC, Ratcliff RM. A novel bocavirus associated with acute gastroenteritis in Australian children. PLoS Pathog. 2009;5:e1000391.
Shen W, Deng X, Zou W, Cheng F, Engelhardt JF, Yan Z, et al. Identification and functional analysis of novel nonstructural proteins of human bocavirus 1. J Virol. 2015;89:10097–109.
Chen AY, Cheng F, Lou S, Luo Y, Liu Z, Delwart E, et al. Characterization of the gene expression profile of human bocavirus. Virol. 2010;403:145–54.
Wang Z, Shen W, Cheng F, Deng X, Engelhardt JF, Yan Z, et al. Parvovirus expresses a small noncoding RNA that plays an essential role in virus replication. J Virol. 2017;91:e2375–416.
Kailasa S, Garrison J, Ilyas M, Chipman P, McKenna R, Kantola K, et al. Mapping antigenic epitopes on the human bocavirus capsid. J Virol. 2016;90:4670–80.
Zhao L, Qian Y, Ding Y, Zhu R, Deng J, Wang F, et al. The expression of the capsid protein VP2 from human bocavirus identified in Beijing and the formation of virus-like particles (VLPs) in insect cells. Bing Du Xue Bao. 2009;25:333–8 (in Chinese).
Mietzsch M, Kailasan S, Garrison J, Ilyas M, Chipman P, Kantola K, et al. Structural insights into human bocaparvoviruses. J Virol. 2017;91:e00261–317.
Luo M, Mietzsch M, Chipman P, Song K, Xu C, Spear J, et al. pH-induced conformational changes of human bocavirus capsids. J Virol. 2021;95:e02329–420.
Kantola K, Hedman L, Allander T, Jartti T, Lehtinen P, Ruuskanen O, et al. Serodiagnosis of human bocavirus infection. Clin Infect Dis. 2008;46:540–6.
Li X, Kantola K, Hedman L, Arku B, Hedman K, Söderlund-Venermo M. Original antigenic sin with human bocaviruses 1–4. J Gen Virol. 2015;96:3099–108.
Zhao L, Qian Y, Zhu R, Deng J, Wang F, Li Y. Genomic sequence analysis for human Bocavirus circulating in Beijing by bioinformatics. Zhonghua Weishengwuxue He Mianyixue Zazhi. 2007;27:389–93 (in Chinese).
Zhao H, Zhao L, Sun Y, Qian Y, Liu L, Jia LP, et al. Detection of a bocavirus circular genome in fecal specimens from children with acute diarrhea in Beijing, China. PLoS One. 2012;7:e48980.
Zhao L, Qian Y, Dong H, Zhu R, Deng J, Li Y, et al. Prokaryotic expression and antigenicity of the capsid protein VP2 from human bocavirus identified in Beijing. Zhonghua Weishengwuxue He Mianyixue Zazhi. 2008;28:1–5 (in Chinese).
Desai M, Di R, Fan H. Application of biolayer interferometry (BLI) for studying protein-protein interactions in transcription. J Vis Exp. 2019. https://doi.org/10.3791/59687.
Li X, Chen B, Zhang S, Li X, Chang J, Tang Y, et al. Rapid detection of respiratory pathogens for community-acquired pneumonia by capillary electrophoresis-based multiplex PCR. SLAS Technol. 2019;24:105–16.
Deng ZH, Hao YX, Yao LH, Xie ZP, Gao HC, Xie LY, et al. Immunogenicity of recombinant human bocavirus-1, 2 VP2 gene virus-like particles in mice. Immunology. 2014;142:58–66.
Acknowledgements
We would like to thank the Affiliated Children's Hospital and Capital Institute of Pediatrics staff for collecting the clinical samples, and the children and their parents who supported our research work. We would like to thank Editage (http://www.editage.cn) for language editing.
Funding
This work was supported by the Beijing Natural Science Foundation (7192029), the National Natural Science Foundation of China (82172277), and the Beijing Municipal Commission of Health (2060399 PXM2017_026268_00005_00254486).
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DR contributed to methodology, formal analysis, and writing of the original draft. XYP contributed to validation, reviewing and editing. WF and ZYT contributed to data curation and methodology. SPD contributed to software. ZRN contributed to investigation. SY, LLY, JLP, and DHJ contributed to resources. ZH contributed to visualization. QCF contributed to supervision, project administration, reviewing and editing. ZLQ contributed to conceptualization, supervision, reviewing and editing, and funding acquisition. All the authors approved the final version of the manuscript.
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The research was approved by the Ethics Committee of the Capital Institute of Pediatrics (approval number: SHERLLM2019013) as a retrospective study.
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De, R., Xu, YP., Wang, F. et al. Human bocavirus 1 and 2 genotype-specific antibodies for rapid antigen testing in pediatric patients with acute respiratory infections. World J Pediatr 19, 1009–1016 (2023). https://doi.org/10.1007/s12519-023-00697-8
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DOI: https://doi.org/10.1007/s12519-023-00697-8