Skip to main content
Top
Published in: Virology Journal 1/2017

Open Access 01-12-2017 | Research

Comparison of serological assays to titrate Hantaan and Seoul hantavirus-specific antibodies

Authors: Weihong Li, Shouchun Cao, Quanfu Zhang, Jiandong Li, Shuo Zhang, Wei Wu, Jing Qu, Chuan Li, Mifang Liang, Dexin Li

Published in: Virology Journal | Issue 1/2017

Login to get access

Abstract

Background

Hantaan and Seoul viruses, in the Hantavirus genus, are known to cause hemorrhagic fever with renal syndrome (HFRS). The plaque reduction neutralization test (PRNT), as conventional neutralization test for hantaviruses, is laborious and time-consuming. Alternatives to PRNT for hantaviruses are required.

Methods

In this study, the methods for Hantaan and Seoul viruses serological typing including microneutralization test (MNT), pseudoparticle neutralization test (PPNT) and immunofluorescence assay based on viral glycoproteins (IFA-GP) were developed and compared with PRNT using a panel of 74 sera including 44 convalescent sera of laboratory confirmed HFRS patients and 30 patients sera of non-hantavirus infection. Antibody titres and serotyping obtained with different methods above were analyzed by paired-t, linear correlation, McNemar χ2 and Kappa agreement tests.

Results

Antibody titres obtained with MNT50, PPNT50 and IFA-GP were significantly correlated with that obtained with PRNT50 (p < 0.001). GMT determined by PPNT50 was statistically higher than that determined by PRNT50 (p < 0.001), while GMT determined by MNT50 and IFA-GP were equal with (p > 0.05) and less than (p < 0.001) that obtained with PRNT50 respectively. Serotyping obtained with MNT50 and PRNT50, PPNT50 and PRNT50 were highly consistent (p < 0.001), whereas that obtained with IFA-GP and PRNT50 were moderately consistent (p < 0.001). There were no significant differences for serotyping between PRNT50 and MNT50, as well as PRNT50 and PPNT50 (p > 0.05). IFA-GP was less sensitive than PRNT50 and MNT50 for serotyping of hantaviruses infection (p < 0.05). However, for 79.5% (35/44) samples, serotyping determined by IFA-GP and PRNT50 were consistent.

Conclusions

MNT50 and PPNT50 both can be used as simple and rapid alternatives to PRNT50, and MNT50 is more specific while PPNT50 is more sensitive than other assays for neutralizing antibody determination. So far, this work has been the most comprehensive comparison of alternatives to PRNT.
Literature
1.
go back to reference Schmaljohn CS, Hasty SE, Dalrymple JM, et al. Antigenic and genetic properties of viruses linked to hemorrhagic fever with renal syndrome. Science. 1985;227(4690):1041–4.CrossRefPubMed Schmaljohn CS, Hasty SE, Dalrymple JM, et al. Antigenic and genetic properties of viruses linked to hemorrhagic fever with renal syndrome. Science. 1985;227(4690):1041–4.CrossRefPubMed
3.
go back to reference Walter CT, Barr JN. Recent advances in the molecular and cellular biology of bunyaviruses. J Gen Virol. 2011;92:2467–84.CrossRefPubMed Walter CT, Barr JN. Recent advances in the molecular and cellular biology of bunyaviruses. J Gen Virol. 2011;92:2467–84.CrossRefPubMed
4.
go back to reference Muyangwa M, Martynova EV, Khaiboullina SF, et al. Hantaviral proteins: structure, functions, and role in hantavirus infection. Front Microbiol. 2015;6:1326.CrossRefPubMedPubMedCentral Muyangwa M, Martynova EV, Khaiboullina SF, et al. Hantaviral proteins: structure, functions, and role in hantavirus infection. Front Microbiol. 2015;6:1326.CrossRefPubMedPubMedCentral
6.
go back to reference Arikawa J, Schmaljohn AL, Dalrymple JM, et al. Characterization of Hantaan virus envelope glycoprotein antigenic determinants defined by monoclonal antibodies. J Gen Virol. 1989;70:615–24.CrossRefPubMed Arikawa J, Schmaljohn AL, Dalrymple JM, et al. Characterization of Hantaan virus envelope glycoprotein antigenic determinants defined by monoclonal antibodies. J Gen Virol. 1989;70:615–24.CrossRefPubMed
7.
go back to reference Dantas JR Jr, Okuno Y, Asada H, et al. Characterization of glycoproteins of viruses causing hemorrhagic fever with renal syndrome (HFRS) using monoclonal antibodies. Virology. 1986;151(2):379–84.CrossRefPubMed Dantas JR Jr, Okuno Y, Asada H, et al. Characterization of glycoproteins of viruses causing hemorrhagic fever with renal syndrome (HFRS) using monoclonal antibodies. Virology. 1986;151(2):379–84.CrossRefPubMed
8.
go back to reference Hooper JW, Custer DM, Thompson E, et al. DNA vaccination with the Hantaan virus M gene protects hamsters against three of four HFRS hantaviruses and elicits a high-titre neutralizing antibody response in rhesus monkeys. J Virol. 2001;75:8469–77.CrossRefPubMedPubMedCentral Hooper JW, Custer DM, Thompson E, et al. DNA vaccination with the Hantaan virus M gene protects hamsters against three of four HFRS hantaviruses and elicits a high-titre neutralizing antibody response in rhesus monkeys. J Virol. 2001;75:8469–77.CrossRefPubMedPubMedCentral
10.
go back to reference Hart CA, Bennett M. Hantavirus infections: epidemiology and pathogenesis. Microbes Infect. 1999;1(14):1229–37.CrossRefPubMed Hart CA, Bennett M. Hantavirus infections: epidemiology and pathogenesis. Microbes Infect. 1999;1(14):1229–37.CrossRefPubMed
11.
go back to reference Song G. Epidemiological progresses of hemorrhagic fever with renal syndrome in China. Chin Med J. 1999;112(5):472–7.PubMed Song G. Epidemiological progresses of hemorrhagic fever with renal syndrome in China. Chin Med J. 1999;112(5):472–7.PubMed
12.
13.
go back to reference Chu YK, Jennings G, Schmaljohn A, et al. Cross-neutralization of hantaviruses with immune sera from experimentally infected animals and from hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome patients. J Infect Dis. 1995;172(6):1581–4.CrossRefPubMed Chu YK, Jennings G, Schmaljohn A, et al. Cross-neutralization of hantaviruses with immune sera from experimentally infected animals and from hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome patients. J Infect Dis. 1995;172(6):1581–4.CrossRefPubMed
14.
go back to reference Lee PW, Gibbs CJ Jr, Gajdusek DC, et al. Serotypic classification of hantaviruses by indirect immunofluorescent antibody and plaque reduction neutralization tests. J Clin Microbiol. 1985;22(6):940–4.PubMedPubMedCentral Lee PW, Gibbs CJ Jr, Gajdusek DC, et al. Serotypic classification of hantaviruses by indirect immunofluorescent antibody and plaque reduction neutralization tests. J Clin Microbiol. 1985;22(6):940–4.PubMedPubMedCentral
15.
go back to reference Yu YX, Yao ZH, An Q, et al. Studies on serotypic classification of viruses of hemorrhagic fever with renal syndrome by plaque reduction neutralization test. Bing Du Xue Bao. 1991;7:18–22. Yu YX, Yao ZH, An Q, et al. Studies on serotypic classification of viruses of hemorrhagic fever with renal syndrome by plaque reduction neutralization test. Bing Du Xue Bao. 1991;7:18–22.
16.
go back to reference Anderson LJ, Hierholzer JC, Bingham PG, et al. Microneutralization test for respiratory syncytial virus based on an enzyme immunoassay. J Clin Microbiol. 1985;22(6):1050–2.PubMedPubMedCentral Anderson LJ, Hierholzer JC, Bingham PG, et al. Microneutralization test for respiratory syncytial virus based on an enzyme immunoassay. J Clin Microbiol. 1985;22(6):1050–2.PubMedPubMedCentral
17.
go back to reference Kenny MT, Albright KL, Sanderson RP. Microneutralization test for the determination of mumps antibody in vero cells. Appl Microbiol. 1970;20(3):371–3.PubMedPubMedCentral Kenny MT, Albright KL, Sanderson RP. Microneutralization test for the determination of mumps antibody in vero cells. Appl Microbiol. 1970;20(3):371–3.PubMedPubMedCentral
18.
go back to reference Mannen K, Mifune K, Reid-Sanden FL, et al. Microneutralization test for rabies virus based on an enzyme immunoassay. J Clin Microbiol. 1987;25(12):2440–2.PubMedPubMedCentral Mannen K, Mifune K, Reid-Sanden FL, et al. Microneutralization test for rabies virus based on an enzyme immunoassay. J Clin Microbiol. 1987;25(12):2440–2.PubMedPubMedCentral
19.
go back to reference Vorndam V, Beltran M. Enzyme-linked immunosorbent assay-format microneutralization test for dengue viruses. Am J Trop Med Hyg. 2002;66(2):208–12.CrossRefPubMed Vorndam V, Beltran M. Enzyme-linked immunosorbent assay-format microneutralization test for dengue viruses. Am J Trop Med Hyg. 2002;66(2):208–12.CrossRefPubMed
20.
go back to reference Benne CA, Harmsen M, De Jong JC, et al. Neutralization enzyme immunoassay for influenza Virus. J Clin Microbiol. 1994;32(4):987–90.PubMedPubMedCentral Benne CA, Harmsen M, De Jong JC, et al. Neutralization enzyme immunoassay for influenza Virus. J Clin Microbiol. 1994;32(4):987–90.PubMedPubMedCentral
22.
go back to reference Hörling J, Lundkvist A, Huggins JW, et al. Antibodies to Puumala virus in humans determined by neutralization test. J Virol Methods. 1992;39(1–2):139–47.CrossRefPubMed Hörling J, Lundkvist A, Huggins JW, et al. Antibodies to Puumala virus in humans determined by neutralization test. J Virol Methods. 1992;39(1–2):139–47.CrossRefPubMed
23.
24.
25.
go back to reference Garcia JM, Lai JC. Production of influenza pseudotyped lentiviral particles and their use in influenza research and diagnosis: an update. Expert Rev Anti-Infect Ther. 2016;9(4):443–55.CrossRef Garcia JM, Lai JC. Production of influenza pseudotyped lentiviral particles and their use in influenza research and diagnosis: an update. Expert Rev Anti-Infect Ther. 2016;9(4):443–55.CrossRef
26.
go back to reference Garcia JM, Lagarde N, Ma ES, et al. Optimization and evaluation of an influenza a (H5) pseudotyped lentiviral particle-based serological assay. J Clin Virol. 2010;47:29–33.CrossRefPubMed Garcia JM, Lagarde N, Ma ES, et al. Optimization and evaluation of an influenza a (H5) pseudotyped lentiviral particle-based serological assay. J Clin Virol. 2010;47:29–33.CrossRefPubMed
27.
go back to reference Hofmann H, Li X, Zhang X, et al. Severe fever with thrombocytopenia virus glycoproteins are targeted by neutralizing antibodies and can use DC-SIGN as a receptor for pH-dependent entry into human and animal cell lines. J Virol. 2013;87(8):4384–94.CrossRefPubMedPubMedCentral Hofmann H, Li X, Zhang X, et al. Severe fever with thrombocytopenia virus glycoproteins are targeted by neutralizing antibodies and can use DC-SIGN as a receptor for pH-dependent entry into human and animal cell lines. J Virol. 2013;87(8):4384–94.CrossRefPubMedPubMedCentral
28.
go back to reference Cifuentes-Muñoz N, Darlix JL, Tischler ND. Development of a lentiviral vector system to study the role of the Andes virus glycoproteins. Virus Res. 2010;153(1):29–35.CrossRefPubMed Cifuentes-Muñoz N, Darlix JL, Tischler ND. Development of a lentiviral vector system to study the role of the Andes virus glycoproteins. Virus Res. 2010;153(1):29–35.CrossRefPubMed
29.
go back to reference Qian Z, Haessler M, Lemos JA, et al. Targeting vascular injury using hantavirus-pseudotyped lentiviral vectors. Mol Ther. 2006;13(4):694–704.CrossRefPubMed Qian Z, Haessler M, Lemos JA, et al. Targeting vascular injury using hantavirus-pseudotyped lentiviral vectors. Mol Ther. 2006;13(4):694–704.CrossRefPubMed
30.
go back to reference Ma M, Kersten DB, Kamrud KI, et al. Murine leukemia virus pseudotypes of La Crosse and Hantaan Bunyaviruses: a system for analysis of cell tropism. Virus Res. 1999;64(1):23–32.CrossRefPubMed Ma M, Kersten DB, Kamrud KI, et al. Murine leukemia virus pseudotypes of La Crosse and Hantaan Bunyaviruses: a system for analysis of cell tropism. Virus Res. 1999;64(1):23–32.CrossRefPubMed
31.
go back to reference Ogino M, Ebihara H, Lee BH, et al. Use of vesicular stomatitis virus pseudotypes bearing hantaan or seoul virus envelope proteins in a rapid and safe neutralization test. Clin Diagn Lab Immunol. 2003;10(1):154–60.PubMedPubMedCentral Ogino M, Ebihara H, Lee BH, et al. Use of vesicular stomatitis virus pseudotypes bearing hantaan or seoul virus envelope proteins in a rapid and safe neutralization test. Clin Diagn Lab Immunol. 2003;10(1):154–60.PubMedPubMedCentral
32.
go back to reference Ray N, Whidby J, Stewart S, et al. Study of Andes virus entry and neutralization using a pseudovirion system. J Virol Methods. 2010;163(2):416–23.CrossRefPubMed Ray N, Whidby J, Stewart S, et al. Study of Andes virus entry and neutralization using a pseudovirion system. J Virol Methods. 2010;163(2):416–23.CrossRefPubMed
33.
go back to reference Higa MM, Petersen J, Hooper J, et al. Efficient production of Hantaan and Puumala pseudovirions for viral tropism and neutralization studies. Virology. 2012;423(2):134–42.CrossRefPubMed Higa MM, Petersen J, Hooper J, et al. Efficient production of Hantaan and Puumala pseudovirions for viral tropism and neutralization studies. Virology. 2012;423(2):134–42.CrossRefPubMed
34.
go back to reference Blight KJ, McKeating JA, Rice CM. Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication. J Virol. 2002;76(24):13001–14.CrossRefPubMedPubMedCentral Blight KJ, McKeating JA, Rice CM. Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication. J Virol. 2002;76(24):13001–14.CrossRefPubMedPubMedCentral
35.
go back to reference Liang MF, Song G, Hang CS, et al. Preliminary study on structure protein of epidemic hemorrhagic fever virus using monoclonal antibodies. Bing Du Xue Bao. 1989;5(3):217–23. Liang MF, Song G, Hang CS, et al. Preliminary study on structure protein of epidemic hemorrhagic fever virus using monoclonal antibodies. Bing Du Xue Bao. 1989;5(3):217–23.
36.
go back to reference Koch J, Liang M, Queitsch I, et al. Human recombinant neutralizing antibodies against hantaan virus G2 protein. Virology. 2003;308:64–73.CrossRefPubMed Koch J, Liang M, Queitsch I, et al. Human recombinant neutralizing antibodies against hantaan virus G2 protein. Virology. 2003;308:64–73.CrossRefPubMed
37.
go back to reference Zhang QF, Li JD, Li WH, et al. Development and application of a two-step MacELISA for the early diagnosis of hemorrhagic fever with renal syndrome. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2008;22(1):6–8.PubMed Zhang QF, Li JD, Li WH, et al. Development and application of a two-step MacELISA for the early diagnosis of hemorrhagic fever with renal syndrome. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2008;22(1):6–8.PubMed
38.
go back to reference Zöller L, Yang S, Gött P, et al. Use of recombinant nucleocapsid proteins of the Hantaan and nephropathia epidemica serotypes of hantaviruses as immunodiagnostic antigens. J Med Virol. 1993;39(3):200–7.CrossRefPubMed Zöller L, Yang S, Gött P, et al. Use of recombinant nucleocapsid proteins of the Hantaan and nephropathia epidemica serotypes of hantaviruses as immunodiagnostic antigens. J Med Virol. 1993;39(3):200–7.CrossRefPubMed
39.
go back to reference Pang Z, Li A, Li J, et al. Comprehensive multiplex one-step real-time TaqMan qRT-PCR assays for detection and quantification of hemorrhagic fever viruses. PLoS One. 2014;9(4):e95635.CrossRefPubMedPubMedCentral Pang Z, Li A, Li J, et al. Comprehensive multiplex one-step real-time TaqMan qRT-PCR assays for detection and quantification of hemorrhagic fever viruses. PLoS One. 2014;9(4):e95635.CrossRefPubMedPubMedCentral
40.
go back to reference Chu YK, Rossi C, Leduc JW, et al. Serological relationships among viruses in the hantavirus genus, family Bunyaviridae. Virology. 1994;198(1):196–204.CrossRefPubMed Chu YK, Rossi C, Leduc JW, et al. Serological relationships among viruses in the hantavirus genus, family Bunyaviridae. Virology. 1994;198(1):196–204.CrossRefPubMed
41.
go back to reference Connor RI, Chen BK, Choe S, et al. Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes. Virology. 1995;206(2):935–44.CrossRefPubMed Connor RI, Chen BK, Choe S, et al. Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes. Virology. 1995;206(2):935–44.CrossRefPubMed
42.
go back to reference Vaheri A, Vapalahti O, Plyusnin A. How to diagnose hantavirus infections and detect them in rodents and insectivores. Rev Med Virol. 2008;18(4):277–88.CrossRefPubMed Vaheri A, Vapalahti O, Plyusnin A. How to diagnose hantavirus infections and detect them in rodents and insectivores. Rev Med Virol. 2008;18(4):277–88.CrossRefPubMed
43.
go back to reference Mattar S, Guzmán C, Figueiredo LT. Diagnosis of hantavirus infection in humans. Expert Rev Anti-Infect Ther. 2015;13(8):939–46.CrossRefPubMed Mattar S, Guzmán C, Figueiredo LT. Diagnosis of hantavirus infection in humans. Expert Rev Anti-Infect Ther. 2015;13(8):939–46.CrossRefPubMed
44.
go back to reference Song G, Hang CS, Liao HX, et al. Antigenic difference between viral strains causing classical and mild types of epidemic hemorrhagic fever with renal syndrome in China. J Infect Dis. 1984;150(6):889–94.CrossRefPubMed Song G, Hang CS, Liao HX, et al. Antigenic difference between viral strains causing classical and mild types of epidemic hemorrhagic fever with renal syndrome in China. J Infect Dis. 1984;150(6):889–94.CrossRefPubMed
Metadata
Title
Comparison of serological assays to titrate Hantaan and Seoul hantavirus-specific antibodies
Authors
Weihong Li
Shouchun Cao
Quanfu Zhang
Jiandong Li
Shuo Zhang
Wei Wu
Jing Qu
Chuan Li
Mifang Liang
Dexin Li
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2017
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-017-0799-0

Other articles of this Issue 1/2017

Virology Journal 1/2017 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.