Characterization of the Monoclonal Antibody and the Immunodominant B-cell Epitope of African Swine Fever Virus PA104R by Using Mouse Model

Overview

Journal Microbiol Spectr

Specialty Microbiology

Date 2024 Feb 2

PMID 38305163

Authors

Qichao Chen

Lixinjie Liu

Shibang Guo

Liang Li

Yifeng Yu

Zhankui Liu

Chen Tan

Huanchun Chen

Xiangru Wang

Affiliations

Soon will be listed here.

Abstract

The African swine fever virus (ASFV) structural protein pA104R is the only histone-like protein encoded by eukaryotic viruses. pA104R is an essential DNA-binding protein required for DNA replication and genome packaging of ASFV, which are vital for pathogen survival and proliferation. pA104R is an important target molecule for diagnosing, treating, and immune prevention of ASFV. This study characterized monoclonal antibodies (mAbs) against pA104R and found them to recognize natural pA104R in ASFV strains with different genotypes, showing high conservation. Confirmation analyses of pA104R epitopes using mAbs indicated the presence of immunodominant B-cell epitopes, and further characterization showed the high antigenic index and surface accessibility coefficients of the identified epitope. Furthermore, the pA104R protein functions through the polar interactions between the binding amino acid sites; however, these interactions may be blocked by the recognition of generated mAbs. Characterizing the immunodominant B-cell epitope of the ASFV critical proteins, such as pA104R, may contribute to developing sensitive diagnostic tools and vaccine candidate targets.African swine fever (ASF) is a highly pathogenic, lethal, and contagious viral disease affecting domestic pigs and wild boars. As no effective vaccine or other treatments have been developed, the control of African swine fever virus (ASFV) relies heavily on virus detection and diagnosis. A potential serological target is the structural protein pA104R. However, the molecular basis of pA104R antigenicity remains unclear, and a specific monoclonal antibody (mAb) against this protein is still unavailable. In this study, mAbs against pA104R were characterized and found to recognize natural pA104R in ASFV strains with different genotypes. In addition, confirmation analyses of pA104R epitopes using mAbs indicated the presence of immunodominant B-cell epitopes, and further characterization showed the high antigenic index and surface accessibility coefficients of the identified epitope. Characteristics of the immunodominant B-cell epitope of ASFV proteins, such as pA104R, may contribute to developing sensitive diagnostic tools and identifying vaccine candidate targets.

Citing Articles

Advancement in the Antigenic Epitopes and Vaccine Adjuvants of African Swine Fever Virus.

Wu Q, Li C, Zhu B, Zhu J, Yang K, Liu Z Pathogens. 2024; 13(8).

PMID: 39204306 PMC: 11357537. DOI: 10.3390/pathogens13080706.

References

Chen Q, Li L, Guo S, Liu Z, Liu L, Tan C . African swine fever virus pA104R protein acts as a suppressor of type I interferon signaling. Front Microbiol. 2023; 14:1169699. PMC: 10119599. DOI: 10.3389/fmicb.2023.1169699. View

Simoes M, Rino J, Pinheiro I, Martins C, Ferreira F . Alterations of Nuclear Architecture and Epigenetic Signatures during African Swine Fever Virus Infection. Viruses. 2015; 7(9):4978-96. PMC: 4584302. DOI: 10.3390/v7092858. View

Mighell E, Ward M . African Swine Fever spread across Asia, 2018-2019. Transbound Emerg Dis. 2021; 68(5):2722-2732. DOI: 10.1111/tbed.14039. View

Reis A, Parkhouse R, Penedos A, Martins C, Leitao A . Systematic analysis of longitudinal serological responses of pigs infected experimentally with African swine fever virus. J Gen Virol. 2007; 88(Pt 9):2426-2434. DOI: 10.1099/vir.0.82857-0. View

Carlson J, Zani L, Schwaiger T, Nurmoja I, Viltrop A, Vilem A . Simplifying sampling for African swine fever surveillance: Assessment of antibody and pathogen detection from blood swabs. Transbound Emerg Dis. 2017; 65(1):e165-e172. DOI: 10.1111/tbed.12706. View

Lin X, Zhao J, Qian J, Mao Y, Pan J, Li L . Identification of immunodominant B- and T-cell combined epitopes in outer membrane lipoproteins LipL32 and LipL21 of Leptospira interrogans. Clin Vaccine Immunol. 2010; 17(5):778-83. PMC: 2863375. DOI: 10.1128/CVI.00405-09. View

Sastre P, Gallardo C, Monedero A, Ruiz T, Arias M, Sanz A . Development of a novel lateral flow assay for detection of African swine fever in blood. BMC Vet Res. 2016; 12:206. PMC: 5025629. DOI: 10.1186/s12917-016-0831-4. View

Salas M, Andres G . African swine fever virus morphogenesis. Virus Res. 2012; 173(1):29-41. DOI: 10.1016/j.virusres.2012.09.016. View

VanderWaal K, Deen J . Global trends in infectious diseases of swine. Proc Natl Acad Sci U S A. 2018; 115(45):11495-11500. PMC: 6233110. DOI: 10.1073/pnas.1806068115. View

10.

Bi C, Shao Z, Li J, Weng C . Identification of novel epitopes targeting non-structural protein 2 of PRRSV using monoclonal antibodies. Appl Microbiol Biotechnol. 2019; 103(6):2689-2699. DOI: 10.1007/s00253-019-09665-7. View

11.

Wozniakowski G, Kozak E, Kowalczyk A, Lyjak M, Pomorska-Mol M, Niemczuk K . Current status of African swine fever virus in a population of wild boar in eastern Poland (2014-2015). Arch Virol. 2015; 161(1):189-95. PMC: 4698278. DOI: 10.1007/s00705-015-2650-5. View

12.

Tao D, Sun D, Liu Y, Wei S, Yang Z, An T . One year of African swine fever outbreak in China. Acta Trop. 2020; 211:105602. DOI: 10.1016/j.actatropica.2020.105602. View

13.

Liu R, Sun Y, Chai Y, Li S, Li S, Wang L . The structural basis of African swine fever virus pA104R binding to DNA and its inhibition by stilbene derivatives. Proc Natl Acad Sci U S A. 2020; 117(20):11000-11009. PMC: 7245070. DOI: 10.1073/pnas.1922523117. View

14.

Cwynar P, Stojkov J, Wlazlak K . African Swine Fever Status in Europe. Viruses. 2019; 11(4). PMC: 6521326. DOI: 10.3390/v11040310. View

15.

Zhang P, Lv L, Sun H, Li S, Fan H, Wang X . Identification of linear B cell epitope on gB, gC, and gE proteins of porcine pseudorabies virus using monoclonal antibodies. Vet Microbiol. 2019; 234:83-91. DOI: 10.1016/j.vetmic.2019.05.013. View

16.

Collins A . IgG subclass co-expression brings harmony to the quartet model of murine IgG function. Immunol Cell Biol. 2016; 94(10):949-954. DOI: 10.1038/icb.2016.65. View

17.

Zhou X, Li N, Luo Y, Liu Y, Miao F, Chen T . Emergence of African Swine Fever in China, 2018. Transbound Emerg Dis. 2018; 65(6):1482-1484. DOI: 10.1111/tbed.12989. View

18.

Alejo A, Matamoros T, Guerra M, Andres G . A Proteomic Atlas of the African Swine Fever Virus Particle. J Virol. 2018; 92(23). PMC: 6232493. DOI: 10.1128/JVI.01293-18. View

19.

Crameri G, Wang L, Morrissy C, White J, Eaton B . A rapid immune plaque assay for the detection of Hendra and Nipah viruses and anti-virus antibodies. J Virol Methods. 2001; 99(1-2):41-51. DOI: 10.1016/s0166-0934(01)00377-9. View

20.

Gutierrez-Castaneda B, Reis A, Corteyn A, Parkhouse R, Kollnberger S . Expression, cellular localization and antibody responses of the African swine fever virus genes B602L and K205R. Arch Virol. 2008; 153(12):2303-6. DOI: 10.1007/s00705-008-0246-z. View