Dataset Information

Development of a Monoclonal Antibody Against Porcine CD163 SRCR5 Domain Which Partially Blocks Infection of PRRSV.

ABSTRACT: Porcine reproductive and respiratory syndrome virus (PRRSV), which seriously endangers the world pig industry, invades host cells through receptor-mediated endocytosis involving clathrin. CD163 is an essential receptor for PRRSV during its infection of cells. The scavenger receptor cysteine-rich 5 (SRCR5) domain of the CD163 molecule is necessary for PRRSV infection, and interacts with glycoproteins GP2a and GP4 of PRRSV, allowing the virus to infect the host cells. In this study, a monoclonal antibody (mAb) against the SRCR5-6 region of porcine CD163 was developed, and the target epitope of the mAb was determined as ⁴⁹⁷TWGTVCDSDF⁵⁰⁶, which is directly adjacent to the ligand-binding pocket (LBP) domain (487-495aa) of CD163. Further study indicated that the mAb could partially block PRRSV infection of its target cells, pulmonary alveolar macrophages. The mAb developed in the study may provide a foundation of antiviral therapy for PRRSV.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7674782 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Development of a Monoclonal Antibody Against Porcine CD163 SRCR5 Domain Which Partially Blocks Infection of PRRSV.

Zhang Yujiao Y Zhang Kuan K Zheng Hao H Liu Changlong C Jiang Yifeng Y Du Nannan N Li Liwei L Li Guoxin G Yu Lingxue L Zhou Yanjun Y Tong Wu W Zhao Kuan K Tong Guangzhi G Gao Fei F

Frontiers in veterinary science 20201105

Porcine reproductive and respiratory syndrome virus (PRRSV), which seriously endangers the world pig industry, invades host cells through receptor-mediated endocytosis involving clathrin. CD163 is an essential receptor for PRRSV during its infection of cells. The scavenger receptor cysteine-rich 5 (SRCR5) domain of the CD163 molecule is necessary for PRRSV infection, and interacts with glycoproteins GP2a and GP4 of PRRSV, allowing the virus to infect the host cells. In this study, a monoclonal a ...[more]

PMID: 33251273

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Project description:Neutralizing antibodies (NAbs) have attracted attention as tools for achieving PRRSV control and prevention, but viral antigenic variation undermines the abilities of NAbs elicited by attenuated PRRSV vaccines to confer full protection against heterogeneous PRRSV field isolates. As demonstrated in this study, the monoclonal antibody (mAb) mAb-PN9cx3 exhibited broad-spectrum recognition and neutralizing activities against PRRSV-1 and PRRSV-2 strains in vitro. Furthermore, in vivo experiments revealed that the administration of two 10-mg doses of mAb-PN9cx3 before and after the inoculation of piglets with heterologous PRRSV isolates (HP-PRRSV-JXA1 or PRRSV NADC30-like strain HNhx) resulted in significant reduction of the PRRSV-induced pulmonary pathological changes and virus loads in porcine alveolar macrophages (PAMs) compared with the results obtained with mAb-treated isotype controls. Moreover, minimal hilar lymph node PRRSV antigen levels were observed in mAb-PN9cx3-treated piglets. A transcriptome profile analysis of PAMs extracted from lung tissues of piglets belonging to different groups (except for antibody-isotype controls) indicated that mAb-PN9cx3 treatment reversed the PRRSV infection-induced alterations in expression profiles. A gene ontology (GO) enrichment analysis of these genes traced their functions to pathways that included the immune response, inflammatory response, and response to steroid hormone, and their functions in oogenesis and positive regulation of angiogenesis have been implicated in PRRSV pathogenesis. Overall, NADC30-like HNhx infection affected more gene pathways than HP-PRRSV infection. In conclusion, our research describes a novel immunologic approach involving the use of mAbs that confer cross-protection against serious illness resulting from infection with heterogeneous PRRSV-2 isolates, which is a feat that has not yet been achieved through vaccination. Ultimately, mAb-PN9cx3 will be a powerful addition to our current arsenal for achieving PRRSV prevention and eradication.

Dataset Information

Development of a Monoclonal Antibody Against Porcine CD163 SRCR5 Domain Which Partially Blocks Infection of PRRSV.

Publications

Development of a Monoclonal Antibody Against Porcine CD163 SRCR5 Domain Which Partially Blocks Infection of PRRSV.

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