Secreted Nonstructural Protein 3 is a Pathogenic Determinant of Orbivirus
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| Format: | Artículo Open Access |
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Wiley
2026
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| _version_ | 1867010159628255232 |
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| author | Junyong Guan Dong Zhou Ran Shao Xing Liu Jin Peng Yingran Huang Shuhui Qi Cankun Xi Menghang Wang Bin Sun Yinglin Qi Xin Yin |
| author_facet | Junyong Guan Dong Zhou Ran Shao Xing Liu Jin Peng Yingran Huang Shuhui Qi Cankun Xi Menghang Wang Bin Sun Yinglin Qi Xin Yin Junyong Guan Dong Zhou Ran Shao Xing Liu Jin Peng Yingran Huang Shuhui Qi Cankun Xi Menghang Wang Bin Sun Yinglin Qi Xin Yin |
| collection | Wiley Open Access |
| contents | Secreted Nonstructural Protein 3 is a Pathogenic Determinant of Orbivirus Junyong Guan Dong Zhou Ran Shao Xing Liu Jin Peng Yingran Huang Shuhui Qi Cankun Xi Menghang Wang Bin Sun Yinglin Qi Xin Yin Advanced Science ABSTRACT Orbivirus is a genus of double‐stranded RNA viruses that infect a broad spectrum of arthropods and vertebrates. Hemorrhage across different organs is a hallmark pathological feature of orbivirus infection, as exemplified by the bluetongue virus (BTV); however, the underlying mechanisms for this feature remain unclear. This study unravels a previously unrecognized extracellular role of orbivirus nonstructural protein 3 (NS3), which hijacks the conventional secretion pathway and utilizes phosphatidylinositol (4,5)‐bisphosphate to travel across the plasma membrane, ultimately inducing vascular permeability and leakage. Site‐directed mutagenesis reveals a conserved lysine or arginine residue adjacent to the second transmembrane domain of orbivirus NS3 as being critical for secretion. Notably, a single lysine mutation impairing NS3 secretion in BTV has no effect on viral infection in vitro but abolishes vascular leakage in the spleen and lungs, rendering the virus completely avirulent in AG129 mice. This study reveals the extracellular functions of orbivirus NS3, providing critical novel insights into the molecular mechanisms driving the hemorrhagic pathology characteristic of orbivirus infections. 10.1002/advs.75255 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/advs.75255 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_advs_75255 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2026 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Secreted Nonstructural Protein 3 is a Pathogenic Determinant of Orbivirus Junyong Guan Dong Zhou Ran Shao Xing Liu Jin Peng Yingran Huang Shuhui Qi Cankun Xi Menghang Wang Bin Sun Yinglin Qi Xin Yin Advanced Science Secreted Nonstructural Protein 3 is a Pathogenic Determinant of Orbivirus Junyong Guan Dong Zhou Ran Shao Xing Liu Jin Peng Yingran Huang Shuhui Qi Cankun Xi Menghang Wang Bin Sun Yinglin Qi Xin Yin Advanced Science ABSTRACT Orbivirus is a genus of double‐stranded RNA viruses that infect a broad spectrum of arthropods and vertebrates. Hemorrhage across different organs is a hallmark pathological feature of orbivirus infection, as exemplified by the bluetongue virus (BTV); however, the underlying mechanisms for this feature remain unclear. This study unravels a previously unrecognized extracellular role of orbivirus nonstructural protein 3 (NS3), which hijacks the conventional secretion pathway and utilizes phosphatidylinositol (4,5)‐bisphosphate to travel across the plasma membrane, ultimately inducing vascular permeability and leakage. Site‐directed mutagenesis reveals a conserved lysine or arginine residue adjacent to the second transmembrane domain of orbivirus NS3 as being critical for secretion. Notably, a single lysine mutation impairing NS3 secretion in BTV has no effect on viral infection in vitro but abolishes vascular leakage in the spleen and lungs, rendering the virus completely avirulent in AG129 mice. This study reveals the extracellular functions of orbivirus NS3, providing critical novel insights into the molecular mechanisms driving the hemorrhagic pathology characteristic of orbivirus infections. 10.1002/advs.75255 http://creativecommons.org/licenses/by/4.0/ |
| title | Secreted Nonstructural Protein 3 is a Pathogenic Determinant of Orbivirus |
| topic | Advanced Science |
| url | https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.75255 |