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CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression

CD163 has been identified as the essential receptor for Porcine reproductive and respiratory syndrome (PRRSV), a major etiologic agent of pigs. Scavenger receptor cysteine-rich domain 5–9 (SRCR5–9) in CD163 was shown to be responsible for the virus interaction. In this study, monoclonal antibodies (...

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Autores principales: Xu, Huiling, Liu, Zehui, Zheng, Suya, Han, Guangwei, He, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711879/
https://www.ncbi.nlm.nih.gov/pubmed/33050150
http://dx.doi.org/10.3390/vaccines8040592
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author Xu, Huiling
Liu, Zehui
Zheng, Suya
Han, Guangwei
He, Fang
author_facet Xu, Huiling
Liu, Zehui
Zheng, Suya
Han, Guangwei
He, Fang
author_sort Xu, Huiling
collection PubMed
description CD163 has been identified as the essential receptor for Porcine reproductive and respiratory syndrome (PRRSV), a major etiologic agent of pigs. Scavenger receptor cysteine-rich domain 5–9 (SRCR5–9) in CD163 was shown to be responsible for the virus interaction. In this study, monoclonal antibodies (mAbs) 6E8 and 9A10 against SRCR5–9 were selected based on the significant activity to inhibit PRRSV infection in Porcine Alveolar Macrophage (PAMs) and Marc-145. Both mAbs are capable of blocking variable PRRSV strains in a dose-dependent manner. Meanwhile, as candidates for both prevention and therapeutics, the antibodies successfully inhibit PRRSV infection and the related NF-κB pathway either before or after virus attachment. Besides, the antibody treatment with either mAb leads to a remarkable decrease of CD163 transcription in PAMs and Marc-145. It is potentially caused by the excessive accumulation of membrane associated CD163 due to the failure in CD163 cleavage with the antibody binding. Further, conformational epitopes targeted by 6E8 and 9A10 are identified to be spanning residues (570)SXDVGXV(576) in SRCR5 and Q(797) in SRCR7, respectively. CD163 with mutated epitopes expressed in 3D4 cells fails to support PRRSV infection while wild type CD163 recovers PRRSV infection, indicating the critical role of these residues in PRRSV invasion. These findings promote the understanding in the interaction between PRRSV and the receptor and provide novel broad antiviral strategies for PRRSV prevention and treatment via alternative mechanisms.
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spelling pubmed-77118792020-12-04 CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression Xu, Huiling Liu, Zehui Zheng, Suya Han, Guangwei He, Fang Vaccines (Basel) Article CD163 has been identified as the essential receptor for Porcine reproductive and respiratory syndrome (PRRSV), a major etiologic agent of pigs. Scavenger receptor cysteine-rich domain 5–9 (SRCR5–9) in CD163 was shown to be responsible for the virus interaction. In this study, monoclonal antibodies (mAbs) 6E8 and 9A10 against SRCR5–9 were selected based on the significant activity to inhibit PRRSV infection in Porcine Alveolar Macrophage (PAMs) and Marc-145. Both mAbs are capable of blocking variable PRRSV strains in a dose-dependent manner. Meanwhile, as candidates for both prevention and therapeutics, the antibodies successfully inhibit PRRSV infection and the related NF-κB pathway either before or after virus attachment. Besides, the antibody treatment with either mAb leads to a remarkable decrease of CD163 transcription in PAMs and Marc-145. It is potentially caused by the excessive accumulation of membrane associated CD163 due to the failure in CD163 cleavage with the antibody binding. Further, conformational epitopes targeted by 6E8 and 9A10 are identified to be spanning residues (570)SXDVGXV(576) in SRCR5 and Q(797) in SRCR7, respectively. CD163 with mutated epitopes expressed in 3D4 cells fails to support PRRSV infection while wild type CD163 recovers PRRSV infection, indicating the critical role of these residues in PRRSV invasion. These findings promote the understanding in the interaction between PRRSV and the receptor and provide novel broad antiviral strategies for PRRSV prevention and treatment via alternative mechanisms. MDPI 2020-10-09 /pmc/articles/PMC7711879/ /pubmed/33050150 http://dx.doi.org/10.3390/vaccines8040592 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xu, Huiling
Liu, Zehui
Zheng, Suya
Han, Guangwei
He, Fang
CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression
title CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression
title_full CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression
title_fullStr CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression
title_full_unstemmed CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression
title_short CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression
title_sort cd163 antibodies inhibit prrsv infection via receptor blocking and transcription suppression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711879/
https://www.ncbi.nlm.nih.gov/pubmed/33050150
http://dx.doi.org/10.3390/vaccines8040592
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