Myosin light chain 3 serves as a receptor for nervous necrosis virus entry into host cells via the macropinocytosis pathway
Nodaviridae infections cause severe mortality in insects and fish, with nervous necrosis virus (NNV) posing significant threats to global fish populations. However, the host factors involved in NNV entry remain poorly understood. We identify myosin light chain 3 from marine medaka (Oryzias melastigm...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/104772 |
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| author | Lan Yao Wanwan Zhang Xiaogang Yang Meisheng Yi Kuntong Jia |
| author_facet | Lan Yao Wanwan Zhang Xiaogang Yang Meisheng Yi Kuntong Jia |
| author_sort | Lan Yao |
| collection | DOAJ |
| description | Nodaviridae infections cause severe mortality in insects and fish, with nervous necrosis virus (NNV) posing significant threats to global fish populations. However, the host factors involved in NNV entry remain poorly understood. We identify myosin light chain 3 from marine medaka (Oryzias melastigma) (MmMYL3) as a novel receptor for red-spotted grouper NNV (RGNNV), facilitating internalization via macropinocytosis. MmMYL3 directly binds the RGNNV capsid protein (CP), which depends on the arm and S domains of CP and the EF-hand2 domain of MmMYL3. In vitro experiments showed that MmMYL3 siRNA, protein, anti-MYL3 antibodies, or the arm domain synthetic peptides blocked RGNNV entry. Moreover, in vivo administration of MmMYL3 protein also inhibited RGNNV infection. Ectopic MmMYL3 expression enabled RGNNV internalization into resistant cells. Notably, MmMYL3 facilitated RGNNV internalization through the macropinocytosis pathway via the IGF1R-Rac1/Cdc42 axis. Collectively, our findings underscore MYL3’s crucial role in NNV entry and its potential as an antiviral target. |
| format | Article |
| id | doaj-art-fffc7027e3be454caede6878cb91f9df |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-fffc7027e3be454caede6878cb91f9df2025-08-20T03:29:39ZengeLife Sciences Publications LtdeLife2050-084X2025-06-011310.7554/eLife.104772Myosin light chain 3 serves as a receptor for nervous necrosis virus entry into host cells via the macropinocytosis pathwayLan Yao0https://orcid.org/0009-0003-6725-4195Wanwan Zhang1Xiaogang Yang2Meisheng Yi3Kuntong Jia4https://orcid.org/0000-0001-7674-9454School of Marine Sciences, Sun Yat-sen University, Zhuhai, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Guangzhou, ChinaSchool of Marine Sciences, Sun Yat-sen University, Zhuhai, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Guangzhou, ChinaSchool of Marine Sciences, Sun Yat-sen University, Zhuhai, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Guangzhou, ChinaSchool of Marine Sciences, Sun Yat-sen University, Zhuhai, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Guangzhou, ChinaSchool of Marine Sciences, Sun Yat-sen University, Zhuhai, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Guangzhou, ChinaNodaviridae infections cause severe mortality in insects and fish, with nervous necrosis virus (NNV) posing significant threats to global fish populations. However, the host factors involved in NNV entry remain poorly understood. We identify myosin light chain 3 from marine medaka (Oryzias melastigma) (MmMYL3) as a novel receptor for red-spotted grouper NNV (RGNNV), facilitating internalization via macropinocytosis. MmMYL3 directly binds the RGNNV capsid protein (CP), which depends on the arm and S domains of CP and the EF-hand2 domain of MmMYL3. In vitro experiments showed that MmMYL3 siRNA, protein, anti-MYL3 antibodies, or the arm domain synthetic peptides blocked RGNNV entry. Moreover, in vivo administration of MmMYL3 protein also inhibited RGNNV infection. Ectopic MmMYL3 expression enabled RGNNV internalization into resistant cells. Notably, MmMYL3 facilitated RGNNV internalization through the macropinocytosis pathway via the IGF1R-Rac1/Cdc42 axis. Collectively, our findings underscore MYL3’s crucial role in NNV entry and its potential as an antiviral target.https://elifesciences.org/articles/104772myosin light chain 3nervous necrosis virusreceptorsmacropinocytosis |
| spellingShingle | Lan Yao Wanwan Zhang Xiaogang Yang Meisheng Yi Kuntong Jia Myosin light chain 3 serves as a receptor for nervous necrosis virus entry into host cells via the macropinocytosis pathway eLife myosin light chain 3 nervous necrosis virus receptors macropinocytosis |
| title | Myosin light chain 3 serves as a receptor for nervous necrosis virus entry into host cells via the macropinocytosis pathway |
| title_full | Myosin light chain 3 serves as a receptor for nervous necrosis virus entry into host cells via the macropinocytosis pathway |
| title_fullStr | Myosin light chain 3 serves as a receptor for nervous necrosis virus entry into host cells via the macropinocytosis pathway |
| title_full_unstemmed | Myosin light chain 3 serves as a receptor for nervous necrosis virus entry into host cells via the macropinocytosis pathway |
| title_short | Myosin light chain 3 serves as a receptor for nervous necrosis virus entry into host cells via the macropinocytosis pathway |
| title_sort | myosin light chain 3 serves as a receptor for nervous necrosis virus entry into host cells via the macropinocytosis pathway |
| topic | myosin light chain 3 nervous necrosis virus receptors macropinocytosis |
| url | https://elifesciences.org/articles/104772 |
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