A Novel Antiviral Protein Derived from <i>Oenanthe javanica</i>: Type I Interferon-Dependent Antiviral Signaling and Its Pharmacological Potential

Pathogenesis-related (PR) proteins produced in plants play a crucial role in self-defense against microbial attacks. Previously, we have identified a novel PR-1-like protein (OPRP) from <i>Oenanthe javanica</i> and examined its pharmacologic relevance and cell signaling in mammalian cell...

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Main Authors: Bo-Ram Jo, Hyun-Soo Kim, Jeong-Won Ahn, Eui-Young Jeoung, Su-Kil Jang, Yeong-Min Yoo, Seong-Soo Joo
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/12/6/835
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author Bo-Ram Jo
Hyun-Soo Kim
Jeong-Won Ahn
Eui-Young Jeoung
Su-Kil Jang
Yeong-Min Yoo
Seong-Soo Joo
author_facet Bo-Ram Jo
Hyun-Soo Kim
Jeong-Won Ahn
Eui-Young Jeoung
Su-Kil Jang
Yeong-Min Yoo
Seong-Soo Joo
author_sort Bo-Ram Jo
collection DOAJ
description Pathogenesis-related (PR) proteins produced in plants play a crucial role in self-defense against microbial attacks. Previously, we have identified a novel PR-1-like protein (OPRP) from <i>Oenanthe javanica</i> and examined its pharmacologic relevance and cell signaling in mammalian cells. Purified full-length OPRP protein significantly increased toll-like receptor 4 (TLR4)-dependent expression levels of genes such as inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and CD80. We also found that small peptides (OPRP2 and OPRP3) designed from OPRP remarkably upregulated myxovirus resistance (Mx1), 2′-5′ oligoadenylate sythetase (OAS), and interferon (IFN) α/β genes in mouse splenocytes as well as human epithelial cells. Notably, OPRP protein distinctively activated STAT1 phosphorylation and ISGF-3γ. Interestingly, OPRP2 and OPRP3 were internalized to the cytoplasm and triggered dimerization of STAT1/STAT2, followed by upregulation of type I IFN-dependent antiviral cytokines. Moreover, OPRP1 successfully inhibited viral (Pseudo SARS-CoV-2) entry into host cells. Taken together, we conclude that OPRP and its small peptides (OPRP1 to 3) present a new therapeutic intervention for modulating innate immune activity through type I IFN-dependent antiviral signaling and a new therapeutic approach that drives an antiviral state in non-immune cells by producing antiviral cytokines.
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spelling doaj.art-79b102af10b9486a820910f6b176f8662023-11-23T15:47:47ZengMDPI AGBiomolecules2218-273X2022-06-0112683510.3390/biom12060835A Novel Antiviral Protein Derived from <i>Oenanthe javanica</i>: Type I Interferon-Dependent Antiviral Signaling and Its Pharmacological PotentialBo-Ram Jo0Hyun-Soo Kim1Jeong-Won Ahn2Eui-Young Jeoung3Su-Kil Jang4Yeong-Min Yoo5Seong-Soo Joo6College of Life Science, Gangneung-Wonju National University, 7 Jukheon-gil, Gangneung 25457, Gangwon, KoreaCollege of Life Science, Gangneung-Wonju National University, 7 Jukheon-gil, Gangneung 25457, Gangwon, KoreaCollege of Life Science, Gangneung-Wonju National University, 7 Jukheon-gil, Gangneung 25457, Gangwon, KoreaCollege of Life Science, Gangneung-Wonju National University, 7 Jukheon-gil, Gangneung 25457, Gangwon, KoreaCollege of Life Science, Gangneung-Wonju National University, 7 Jukheon-gil, Gangneung 25457, Gangwon, KoreaCollege of Life Science, Gangneung-Wonju National University, 7 Jukheon-gil, Gangneung 25457, Gangwon, KoreaCollege of Life Science, Gangneung-Wonju National University, 7 Jukheon-gil, Gangneung 25457, Gangwon, KoreaPathogenesis-related (PR) proteins produced in plants play a crucial role in self-defense against microbial attacks. Previously, we have identified a novel PR-1-like protein (OPRP) from <i>Oenanthe javanica</i> and examined its pharmacologic relevance and cell signaling in mammalian cells. Purified full-length OPRP protein significantly increased toll-like receptor 4 (TLR4)-dependent expression levels of genes such as inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and CD80. We also found that small peptides (OPRP2 and OPRP3) designed from OPRP remarkably upregulated myxovirus resistance (Mx1), 2′-5′ oligoadenylate sythetase (OAS), and interferon (IFN) α/β genes in mouse splenocytes as well as human epithelial cells. Notably, OPRP protein distinctively activated STAT1 phosphorylation and ISGF-3γ. Interestingly, OPRP2 and OPRP3 were internalized to the cytoplasm and triggered dimerization of STAT1/STAT2, followed by upregulation of type I IFN-dependent antiviral cytokines. Moreover, OPRP1 successfully inhibited viral (Pseudo SARS-CoV-2) entry into host cells. Taken together, we conclude that OPRP and its small peptides (OPRP1 to 3) present a new therapeutic intervention for modulating innate immune activity through type I IFN-dependent antiviral signaling and a new therapeutic approach that drives an antiviral state in non-immune cells by producing antiviral cytokines.https://www.mdpi.com/2218-273X/12/6/835<i>Oenanthe javanica</i>pathogenesis-related proteintoll-like receptor 4type I interferonantiviral
spellingShingle Bo-Ram Jo
Hyun-Soo Kim
Jeong-Won Ahn
Eui-Young Jeoung
Su-Kil Jang
Yeong-Min Yoo
Seong-Soo Joo
A Novel Antiviral Protein Derived from <i>Oenanthe javanica</i>: Type I Interferon-Dependent Antiviral Signaling and Its Pharmacological Potential
Biomolecules
<i>Oenanthe javanica</i>
pathogenesis-related protein
toll-like receptor 4
type I interferon
antiviral
title A Novel Antiviral Protein Derived from <i>Oenanthe javanica</i>: Type I Interferon-Dependent Antiviral Signaling and Its Pharmacological Potential
title_full A Novel Antiviral Protein Derived from <i>Oenanthe javanica</i>: Type I Interferon-Dependent Antiviral Signaling and Its Pharmacological Potential
title_fullStr A Novel Antiviral Protein Derived from <i>Oenanthe javanica</i>: Type I Interferon-Dependent Antiviral Signaling and Its Pharmacological Potential
title_full_unstemmed A Novel Antiviral Protein Derived from <i>Oenanthe javanica</i>: Type I Interferon-Dependent Antiviral Signaling and Its Pharmacological Potential
title_short A Novel Antiviral Protein Derived from <i>Oenanthe javanica</i>: Type I Interferon-Dependent Antiviral Signaling and Its Pharmacological Potential
title_sort novel antiviral protein derived from i oenanthe javanica i type i interferon dependent antiviral signaling and its pharmacological potential
topic <i>Oenanthe javanica</i>
pathogenesis-related protein
toll-like receptor 4
type I interferon
antiviral
url https://www.mdpi.com/2218-273X/12/6/835
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