A new luciferase immunoprecipitation system assay provided serological evidence for missed diagnosis of severe fever with thrombocytopenia syndrome

Shengyao Chen; Minjun Xu; Xiaoli Wu; Yuan Bai; Junming Shi; Min Zhou; Qiaoli Wu; Shuang Tang; Fei Deng; Bo Qin; Shu Shen

doi:10.1016/j.virs.2022.01.018

February 2022

Citation: Shengyao Chen, Minjun Xu, Xiaoli Wu, Yuan Bai, Junming Shi, Min Zhou, Qiaoli Wu, Shuang Tang, Fei Deng, Bo Qin, Shu Shen. A new luciferase immunoprecipitation system assay provided serological evidence for missed diagnosis of severe fever with thrombocytopenia syndrome .VIROLOGICA SINICA, 2022, 37(1) : 107-114. http://dx.doi.org/10.1016/j.virs.2022.01.018

A new luciferase immunoprecipitation system assay provided serological evidence for missed diagnosis of severe fever with thrombocytopenia syndrome

Shengyao Chen ^a,c ,
Minjun Xu ^d ,
Xiaoli Wu ^a ,
Yuan Bai ^a ,
Junming Shi ^a ,
Min Zhou ^a ,
Qiaoli Wu ^a ,
Shuang Tang ^a ,
Fei Deng ^{a
,,} ,
Bo Qin ^{b,d
,,} ,
Shu Shen ^{a
,,}

a State Key Laboratory of Virology and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China
b Shaoxing Women and Children's Hospital, No. 305 East Street Road, Shaoxing, 312000, China
c University of Chinese Academy of Sciences, Beijing, 100049, China
d Shaoxing People's Hospital, Zhejiang University School of Medicine, Shaoxing, 312000, China

Corresponding author: Fei Deng, df@wh.iov.cn
Bo Qin, qinbo0809@hotmail.com
Shu Shen, shenshu@wh.iov.cn
Received Date: 11 August 2021
Accepted Date: 12 October 2021
Available online: 20 January 2022

Abstract

Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV) infection, was first reported in 2010 in China with an initial fatality of up to 30%. The laboratory confirmation of SFTSV infection in terms of detection of viral RNA or antibody levels is critical for SFTS diagnosis and therapy. In this study, a new luciferase immunoprecipitation system (LIPS) assay based on pREN2 plasmid expressing SFTSV NP gene and tagged with Renilla luciferase (Rluc), was established and used to investigate the levels of antibody responses to SFTSV. Totally 464 serum samples from febrile patients were collected in the hospital of Shaoxing City in Zhejiang Province in 2019. The results showed that 82 of the 464 patients (17.7%) had antibody response to SFTSV, which were further supported by immunofluorescence assays (IFAs). Further, qRT-PCR and microneutralization tests showed that among the 82 positive cases, 15 patients had viremia, 10 patients had neutralizing antibody, and one had both (totally 26 patient). However, none of these patients were diagnosed as SFTS in the hospital probably because of their mild symptoms or subclinical manifestations. All the results indicated that at least the 26 patients having viremia or neutralizing antibody were the missed diagnosis of SFTS cases. The findings suggested the occurrence of SFTS and the SFTS incidence were higher than the reported level in Shaoxing in 2019, and that LIPS may provide an alternative strategy to confirm SFTSV infection in the laboratory.

Electronic Supplementary Material

10.1016j.virs.2022.01.018-ESM.docx
References
1. Burbelo PD, Bren KE, Ching KH, Coleman A, Yang X, Kariu T, Iadarola MJ, Pal U. Antibody profiling of Borrelia burgdorferi infection in horses. Clin Vaccine Immunol. 2011;18:1562-1567.
2. Burbelo PD, Ching KH, Bush ER, Han BL, Iadarola MJ. Antibody-profiling technologies for studying humoral responses to infectious agents. Expert Rev Vaccines. 2010;9:567-578.
3. Burbelo PD, Iadarola MJ, Chaturvedi A. Emerging technologies for the detection of viral infections. Future Virol. 2019;14:39-49.
4. Burbelo PD, Lebovitz EE, Notkins AL. Luciferase immunoprecipitation systems for measuring antibodies in autoimmune and infectious diseases. Transl Res. 2015;165:325-335.
5. Chia WN, Tan CW, Foo R, Kang AEZ, Peng Y, Sivalingam V, Tiu C, Ong XM, Zhu F, Young BE, Chen MI, Tan YJ, Lye DC, Anderson DE, Wang LF. Serological differentiation between COVID-19 and SARS infections. Emerg Microbes Infect. 2020;9:1497-1505.
6. Eliasson M, Andersson R, Olsson A, Wigzell H, Uhlen M. Differential IgG-binding characteristics of staphylococcal protein A, streptococcal protein G, and a chimeric protein AG. J Immunol. 1989;142:575-581.
7. Huang X, Li J, Li A, Wang S, Li D. Epidemiological Characteristics of Severe Fever with Thrombocytopenia Syndrome from 2010 to 2019 in Mainland China. Int J Environ Res Public Health. 2021;18:3092.
8. Huang X, Wang S, Wang X, Lyu Y, Jiang M, Chen D, Li K, Liu J, Xie S, Lyu T, Sun J, Xu P, Cao M, Liang M, Li D. Estimation of the incidence of severe fever with thrombocytopenia syndrome in high endemic areas in China: an inpatient-based retrospective study. BMC Infect Dis. 2018;18:66.
9. Li Z, Hu J, Cui L, Hong Y, Liu J, Li P, Guo X, Liu W, Wang X, Qi X, Wu B, Feng Z, Shen A, Liu X, Zhao H, Tan W, Zhou J, Xing Z, Bao C. Increased Prevalence of Severe Fever with Thrombocytopenia Syndrome in Eastern China Clustered with Multiple Genotypes and Reasserted Virus during 2010-2015. Sci Rep. 2017;7:6503.
10. Maeda Y, Nakane S, Higuchi O, Nakamura H, Komori A, Migita K, Mukaino A, Umeda M, Ichinose K, Tamai M, Kawashiri SY, Sakai W, Yatsuhashi H, Kawakami A, Matsuo H. Ganglionic acetylcholine receptor autoantibodies in patients with autoimmune diseases including primary biliary cirrhosis. Mod Rheumatol. 2017;27:664-668.
11. Matsumoto C, Shinohara N, Furuta RA, Tanishige N, Shimojima M, Matsubayashi K, Nagai T, Tsubaki K, Satake M. Investigation of antibody to severe fever with thrombocytopenia syndrome virus (SFTSV) in blood samples donated in a SFTS-endemic area in Japan. Vox Sang. 2018;113:297-299.
12. Matsuu A, Hamakubo E, Yabuki M. Seroprevalence of severe fever with thrombocytopenia syndrome virus in animals in Kagoshima Prefecture, Japan, and development of Gaussia luciferase immunoprecipitation system to detect specific IgG antibodies. Ticks Tick Borne Dis. 2021;12:101771.
13. Matsuu A, Yokota SI, Ito K, Masatani T. Seroprevalence of Toxoplasma gondii in free-ranging and feral cats on Amami Oshima Island, Japan. J Vet Med Sci. 2017;79:1853-1856.
14. Moming A, Shen S, Fang Y, Zhang J, Zhang Y, Tang S, Li T, Hu Z, wang H, Zhang Y, Wang L, Sun S, Deng F. Evidence of human exposure to Tamdy virus, Northwestern China. Emerg Infect Dis. 2021;(In press).
15. Shen S, Duan X, Wang B, Zhu L, Zhang Y, Zhang J, Wang J, Luo T, Kou C, Liu D, Lv C, Zhang L, Chang C, Su Z, Tang S, Qiao J, Moming A, Wang C, Abudurexiti A, Wang H, Hu Z, Zhang Y, Sun S, Deng F. A novel tick-borne phlebovirus, closely related to severe fever with thrombocytopenia syndrome virus and Heartland virus, is a potential pathogen. Emerg Microbes Infect. 2018;7:95.
16. Sun J, Lu L, Wu H, Yang J, Ren J, Liu Q. The changing epidemiological characteristics of severe fever with thrombocytopenia syndrome in China, 2011-2016. Sci Rep. 2017;7:9236.
17. Uehara A, Tan CW, Mani S, Chua KB, Leo YS, Anderson DE, Wang LF. Serological evidence of human infection by bat orthoreovirus in Singapore. J Med Virol. 2019;91:707-710.
18. Wu H, Wu C, Lu Q, Ding Z, Xue M, Lin J. Spatial-temporal characteristics of severe fever with thrombocytopenia syndrome and the relationship with meteorological factors from 2011 to 2018 in Zhejiang Province, China. PLoS Negl Trop Dis. 2020;14:e0008186.
19. Xiong S, Zhang W, Li M, Xiong Y, Li M, Wang H, Yang D, Peng C, Zheng X. A simple and practical score model for predicting the mortality of severe fever with thrombocytopenia syndrome patients. Medicine (Baltimore). 2016;95:e5708.
20. Yu XJ, Liang MF, Zhang SY, Liu Y, Li JD, Sun YL, Zhang L, Zhang QF, Popov VL, Li C, Qu J, Li Q, Zhang YP, Hai R, Wu W, Wang Q, Zhan FX, Wang XJ, Kan B, Wang SW, Wan KL, Jing HQ, Lu JX, Yin WW, Zhou H, Guan XH, Liu JF, Bi ZQ, Liu GH, Ren J, Wang H, Zhao Z, Song JD, He JR, Wan T, Zhang JS, Fu XP, Sun LN, Dong XP, Feng ZJ, Yang WZ, Hong T, Zhang Y, Walker DH, Wang Y, Li DX. Fever with thrombocytopenia associated with a novel bunyavirus in China. N Engl J Med. 2011;364:1523-1532.
21. Zhang Y, Shen S, Shi J, Su Z, Li M, Zhang W, Li M, Hu Z, Peng C, Zheng X, Deng F. Isolation, characterization, and phylogenic analysis of three new severe fever with thrombocytopenia syndrome bunyavirus strains derived from Hubei Province, China. Virol Sin. 2017;32:89-96.
22. Zhu L, Yin F, Moming A, Zhang J, Wang B, Gao L, Ruan J, Wu Q, Wu N, Wang H, Deng F, Lu G, Shen S. First case of laboratory-confirmed severe fever with thrombocytopenia syndrome disease revealed the risk of SFTSV infection in Xinjiang, China. Emerg Microbes Infect. 2019;8:1122-1125
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