LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase and downregulates its pre-elongation activities.
LGP2 is a RIG-I-like receptor (RLR) known to bind and recognize the intermediate double-stranded RNA (dsRNA) during virus infection and to induce type-I interferon (IFN)-related antiviral innate immune responses. Here, we find that LGP2 inhibits Zika virus (ZIKV) and tick-borne encephalitis virus (T...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-09-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011620&type=printable |
| _version_ | 1797674074504167424 |
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| author | Zhongyuan Tan Jiqin Wu Li Huang Ting Wang Zhenhua Zheng Jianhui Zhang Xianliang Ke Yuan Zhang Yan Liu Hanzhong Wang Jianping Tao Peng Gong |
| author_facet | Zhongyuan Tan Jiqin Wu Li Huang Ting Wang Zhenhua Zheng Jianhui Zhang Xianliang Ke Yuan Zhang Yan Liu Hanzhong Wang Jianping Tao Peng Gong |
| author_sort | Zhongyuan Tan |
| collection | DOAJ |
| description | LGP2 is a RIG-I-like receptor (RLR) known to bind and recognize the intermediate double-stranded RNA (dsRNA) during virus infection and to induce type-I interferon (IFN)-related antiviral innate immune responses. Here, we find that LGP2 inhibits Zika virus (ZIKV) and tick-borne encephalitis virus (TBEV) replication independent of IFN induction. Co-immunoprecipitation (Co-IP) and confocal immunofluorescence data suggest that LGP2 likely colocalizes with the replication complex (RC) of ZIKV by interacting with viral RNA-dependent RNA polymerase (RdRP) NS5. We further verify that the regulatory domain (RD) of LGP2 directly interacts with RdRP of NS5 by biolayer interferometry assay. Data from in vitro RdRP assays indicate that LGP2 may inhibit polymerase activities of NS5 at pre-elongation but not elongation stages, while an RNA-binding-defective LGP2 mutant can still inhibit RdRP activities and virus replication. Taken together, our work suggests that LGP2 can inhibit flavivirus replication through direct interaction with NS5 protein and downregulates its polymerase pre-elongation activities, demonstrating a distinct role of LGP2 beyond its function in innate immune responses. |
| first_indexed | 2024-03-11T21:53:52Z |
| format | Article |
| id | doaj.art-8e0eef66af964ab79456bcbd57222032 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-11T21:53:52Z |
| publishDate | 2023-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-8e0eef66af964ab79456bcbd572220322023-09-26T05:31:14ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-09-01199e101162010.1371/journal.ppat.1011620LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase and downregulates its pre-elongation activities.Zhongyuan TanJiqin WuLi HuangTing WangZhenhua ZhengJianhui ZhangXianliang KeYuan ZhangYan LiuHanzhong WangJianping TaoPeng GongLGP2 is a RIG-I-like receptor (RLR) known to bind and recognize the intermediate double-stranded RNA (dsRNA) during virus infection and to induce type-I interferon (IFN)-related antiviral innate immune responses. Here, we find that LGP2 inhibits Zika virus (ZIKV) and tick-borne encephalitis virus (TBEV) replication independent of IFN induction. Co-immunoprecipitation (Co-IP) and confocal immunofluorescence data suggest that LGP2 likely colocalizes with the replication complex (RC) of ZIKV by interacting with viral RNA-dependent RNA polymerase (RdRP) NS5. We further verify that the regulatory domain (RD) of LGP2 directly interacts with RdRP of NS5 by biolayer interferometry assay. Data from in vitro RdRP assays indicate that LGP2 may inhibit polymerase activities of NS5 at pre-elongation but not elongation stages, while an RNA-binding-defective LGP2 mutant can still inhibit RdRP activities and virus replication. Taken together, our work suggests that LGP2 can inhibit flavivirus replication through direct interaction with NS5 protein and downregulates its polymerase pre-elongation activities, demonstrating a distinct role of LGP2 beyond its function in innate immune responses.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011620&type=printable |
| spellingShingle | Zhongyuan Tan Jiqin Wu Li Huang Ting Wang Zhenhua Zheng Jianhui Zhang Xianliang Ke Yuan Zhang Yan Liu Hanzhong Wang Jianping Tao Peng Gong LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase and downregulates its pre-elongation activities. PLoS Pathogens |
| title | LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase and downregulates its pre-elongation activities. |
| title_full | LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase and downregulates its pre-elongation activities. |
| title_fullStr | LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase and downregulates its pre-elongation activities. |
| title_full_unstemmed | LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase and downregulates its pre-elongation activities. |
| title_short | LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase and downregulates its pre-elongation activities. |
| title_sort | lgp2 directly interacts with flavivirus ns5 rna dependent rna polymerase and downregulates its pre elongation activities |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011620&type=printable |
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