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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2022-06-01
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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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