Identification and Characterization of a Novel Epitope of ASFV-Encoded dUTPase by Monoclonal Antibodies

Deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) of African swine fever virus (ASFV) is an essential enzyme required for efficient virus replication. Previous crystallography data have indicated that dUTPase (E165R) may serve as a therapeutic target for inhibiting ASFV replication; however...

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Autores principales:	Shuai Zhang, Rui Wang, Xiaojing Zhu, Jiaxin Jin, Wenlong Lu, Xuyang Zhao, Bo Wan, Yifei Liao, Qin Zhao, Christopher L. Netherton, Guoqing Zhuang, Aijun Sun, Gaiping Zhang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	African swine fever virus African swine fever dUTPase epitope therapeutic drug Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7bf9166b19c249e1966f43b0568de2ef
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spelling	oai:doaj.org-article:7bf9166b19c249e1966f43b0568de2ef2021-11-25T19:13:04ZIdentification and Characterization of a Novel Epitope of ASFV-Encoded dUTPase by Monoclonal Antibodies10.3390/v131121751999-4915https://doaj.org/article/7bf9166b19c249e1966f43b0568de2ef2021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2175https://doaj.org/toc/1999-4915Deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) of African swine fever virus (ASFV) is an essential enzyme required for efficient virus replication. Previous crystallography data have indicated that dUTPase (E165R) may serve as a therapeutic target for inhibiting ASFV replication; however, the specificity of the targeting site(s) in ASFV dUTPase remains unclear. In this study, 19 mouse monoclonal antibodies (mAbs) were produced, in which four mAbs showed inhibitory reactivity against E165R recombinant protein. Epitope mapping studies indicated that E165R has three major antigenic regions: 100–120 aa, 120–140 aa, and 140–165 aa. Three mAbs inhibited the dUTPase activity of E165R by binding to the highly conserved 149–RGEGRFGSTG–158 amino acid sequence. Interestingly, 8F6 mAb specifically recognized ASFV dUTPase but not Sus scrofa dUTPase, which may be due to structural differences in the amino acids of F151, R153, and F154 in the motif V region. In summary, we developed anti-E165R-specific mAbs, and identified an important antibody-binding antigenic epitope in the motif V of ASFV dUTPase. Our study provides a comprehensive analysis of mAbs that target the antigenic epitope of ASFV dUTPase, which may contribute to the development of novel antibody-based ASFV therapeutics.Shuai ZhangRui WangXiaojing ZhuJiaxin JinWenlong LuXuyang ZhaoBo WanYifei LiaoQin ZhaoChristopher L. NethertonGuoqing ZhuangAijun SunGaiping ZhangMDPI AGarticleAfrican swine fever virusAfrican swine feverdUTPaseepitopetherapeutic drugMicrobiologyQR1-502ENViruses, Vol 13, Iss 2175, p 2175 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	African swine fever virus African swine fever dUTPase epitope therapeutic drug Microbiology QR1-502
spellingShingle	African swine fever virus African swine fever dUTPase epitope therapeutic drug Microbiology QR1-502 Shuai Zhang Rui Wang Xiaojing Zhu Jiaxin Jin Wenlong Lu Xuyang Zhao Bo Wan Yifei Liao Qin Zhao Christopher L. Netherton Guoqing Zhuang Aijun Sun Gaiping Zhang Identification and Characterization of a Novel Epitope of ASFV-Encoded dUTPase by Monoclonal Antibodies
description	Deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) of African swine fever virus (ASFV) is an essential enzyme required for efficient virus replication. Previous crystallography data have indicated that dUTPase (E165R) may serve as a therapeutic target for inhibiting ASFV replication; however, the specificity of the targeting site(s) in ASFV dUTPase remains unclear. In this study, 19 mouse monoclonal antibodies (mAbs) were produced, in which four mAbs showed inhibitory reactivity against E165R recombinant protein. Epitope mapping studies indicated that E165R has three major antigenic regions: 100–120 aa, 120–140 aa, and 140–165 aa. Three mAbs inhibited the dUTPase activity of E165R by binding to the highly conserved 149–RGEGRFGSTG–158 amino acid sequence. Interestingly, 8F6 mAb specifically recognized ASFV dUTPase but not Sus scrofa dUTPase, which may be due to structural differences in the amino acids of F151, R153, and F154 in the motif V region. In summary, we developed anti-E165R-specific mAbs, and identified an important antibody-binding antigenic epitope in the motif V of ASFV dUTPase. Our study provides a comprehensive analysis of mAbs that target the antigenic epitope of ASFV dUTPase, which may contribute to the development of novel antibody-based ASFV therapeutics.
format	article
author	Shuai Zhang Rui Wang Xiaojing Zhu Jiaxin Jin Wenlong Lu Xuyang Zhao Bo Wan Yifei Liao Qin Zhao Christopher L. Netherton Guoqing Zhuang Aijun Sun Gaiping Zhang
author_facet	Shuai Zhang Rui Wang Xiaojing Zhu Jiaxin Jin Wenlong Lu Xuyang Zhao Bo Wan Yifei Liao Qin Zhao Christopher L. Netherton Guoqing Zhuang Aijun Sun Gaiping Zhang
author_sort	Shuai Zhang
title	Identification and Characterization of a Novel Epitope of ASFV-Encoded dUTPase by Monoclonal Antibodies
title_short	Identification and Characterization of a Novel Epitope of ASFV-Encoded dUTPase by Monoclonal Antibodies
title_full	Identification and Characterization of a Novel Epitope of ASFV-Encoded dUTPase by Monoclonal Antibodies
title_fullStr	Identification and Characterization of a Novel Epitope of ASFV-Encoded dUTPase by Monoclonal Antibodies
title_full_unstemmed	Identification and Characterization of a Novel Epitope of ASFV-Encoded dUTPase by Monoclonal Antibodies
title_sort	identification and characterization of a novel epitope of asfv-encoded dutpase by monoclonal antibodies
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7bf9166b19c249e1966f43b0568de2ef
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Identification and Characterization of a Novel Epitope of ASFV-Encoded dUTPase by Monoclonal Antibodies

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