PMID- 30269789 OWN - NLM STAT- MEDLINE DCOM- 20190130 LR - 20190130 IS - 1873-2542 (Electronic) IS - 0378-1135 (Linking) VI - 224 DP - 2018 Oct TI - Phages bearing specific peptides with affinity for porcine reproductive and respiratory syndrome virus GP4 protein prevent cell penetration of the virus. PG - 43-49 LID - S0378-1135(18)30752-1 [pii] LID - 10.1016/j.vetmic.2018.08.027 [doi] AB - Porcine reproductive and respiratory syndrome (PRRS) has caused significant economic losses to the pig industry worldwide over the last 30 years. GP4 is a minor highly glycosylated structural protein composed of 187 and 183 amino acids in types I and II porcine reproductive and respiratory syndrome virus (PRRSV), respectively. The GP4 protein co-localizes with cluster of differentiation 163 (CD163), the major receptor on the target cell membrane, to mediate PRRSV internalization and disassembly. However, it remains to be established whether blocking interactions between GP4 and host cells can inhibit viral proliferation. In the present study, recombinant GP4 protein prepared and purified using the Escherichia coli system effectively recognized PRRSV-positive serum. Phage display biopanning on GP4 protein showed that the specific phages obtained could distinguish PRRSV from the other viruses. The exogenous peptide WHEYPLVWLSGY displayed on one of the candidate phages showed high affinity for GP4 protein and exerted a significant inhibitory effect on PRRSV penetration in vitro. Moreover, the N-terminus of GP4 was predicted as the critical receptor binding site and the beginning of the fifth scavenger receptor cysteine-rich domain of CD163 as the critical ligand recognition site based on sequence alignment and model prediction analyses. The current study expands our understanding of PRRSV GP4 and its receptor CD163 and provides a fresh perspective for the development of novel peptide-based viral inhibition reagents. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Chen, Wanli AU - Chen W AD - College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, 510642, People's Republic of China; Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou, Guangdong Province, 510642, People's Republic of China. FAU - Cui, Jin AU - Cui J AD - College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, 510642, People's Republic of China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, Guangdong Province, 510642, People's Republic of China. FAU - Wang, Jingyu AU - Wang J AD - College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, 510642, People's Republic of China; Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou, Guangdong Province, 510642, People's Republic of China. FAU - Sun, Yankou AU - Sun Y AD - College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, 510642, People's Republic of China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, Guangdong Province, 510642, People's Republic of China. FAU - Ji, Chihai AU - Ji C AD - College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, 510642, People's Republic of China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, Guangdong Province, 510642, People's Republic of China. FAU - Song, Ruyue AU - Song R AD - College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, 510642, People's Republic of China; Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou, Guangdong Province, 510642, People's Republic of China. FAU - Zeng, Yuchen AU - Zeng Y AD - College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, 510642, People's Republic of China; Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou, Guangdong Province, 510642, People's Republic of China. FAU - Pan, Haoming AU - Pan H AD - College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, 510642, People's Republic of China; Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou, Guangdong Province, 510642, People's Republic of China. FAU - Sheng, Jinliang AU - Sheng J AD - College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang Province, 832000, People's Republic of China. FAU - Zhang, Guihong AU - Zhang G AD - College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, 510642, People's Republic of China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, Guangdong Province, 510642, People's Republic of China. Electronic address: guihongzh@scau.edu.cn. FAU - Wang, Heng AU - Wang H AD - College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, 510642, People's Republic of China; Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou, Guangdong Province, 510642, People's Republic of China. Electronic address: wangheng2009@scau.edu.cn. LA - eng PT - Journal Article DEP - 20180829 PL - Netherlands TA - Vet Microbiol JT - Veterinary microbiology JID - 7705469 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CD163 antigen) RN - 0 (Peptides) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Virus) RN - 0 (Recombinant Proteins) RN - 0 (Viral Envelope Proteins) SB - IM MH - Animals MH - Antigens, CD/genetics/metabolism MH - Antigens, Differentiation, Myelomonocytic/genetics/metabolism MH - Bacteriophages/*chemistry/*physiology MH - Binding Sites MH - Cell Line MH - Peptides/*metabolism MH - Porcine Reproductive and Respiratory Syndrome/virology MH - Porcine respiratory and reproductive syndrome virus/*physiology MH - Protein Binding MH - Receptors, Cell Surface/genetics/metabolism MH - Receptors, Virus/metabolism MH - Recombinant Proteins/metabolism MH - Swine MH - *Viral Envelope Proteins/metabolism MH - Virus Internalization OTO - NOTNLM OT - GP4 protein OT - Phage display OT - Porcine reproductive and respiratory syndrome OT - Viral inhibition EDAT- 2018/10/03 06:00 MHDA- 2019/01/31 06:00 CRDT- 2018/10/02 06:00 PHST- 2018/06/27 00:00 [received] PHST- 2018/08/20 00:00 [revised] PHST- 2018/08/28 00:00 [accepted] PHST- 2018/10/02 06:00 [entrez] PHST- 2018/10/03 06:00 [pubmed] PHST- 2019/01/31 06:00 [medline] AID - S0378-1135(18)30752-1 [pii] AID - 10.1016/j.vetmic.2018.08.027 [doi] PST - ppublish SO - Vet Microbiol. 2018 Oct;224:43-49. doi: 10.1016/j.vetmic.2018.08.027. Epub 2018 Aug 29.