USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication
The antiviral activity of host factor apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G, A3G) and its degradation mediated by human immunodeficiency virus type 1 (HIV-1) Vif protein are important topics. Although accumulating evidence indicates the importance of deubiquiti...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/48318 |
| _version_ | 1811181518007042048 |
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| author | Ting Pan Zheng Song Liyang Wu Guangyan Liu Xiancai Ma Zhilin Peng Mo Zhou Liting Liang Bingfeng Liu Jun Liu Junsong Zhang Xuanhong Zhang Ryan Huang Jiacong Zhao Yonghong Li Xuemei Ling Yuewen Luo Xiaoping Tang Weiping Cai Kai Deng Linghua Li Hui Zhang |
| author_facet | Ting Pan Zheng Song Liyang Wu Guangyan Liu Xiancai Ma Zhilin Peng Mo Zhou Liting Liang Bingfeng Liu Jun Liu Junsong Zhang Xuanhong Zhang Ryan Huang Jiacong Zhao Yonghong Li Xuemei Ling Yuewen Luo Xiaoping Tang Weiping Cai Kai Deng Linghua Li Hui Zhang |
| author_sort | Ting Pan |
| collection | DOAJ |
| description | The antiviral activity of host factor apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G, A3G) and its degradation mediated by human immunodeficiency virus type 1 (HIV-1) Vif protein are important topics. Although accumulating evidence indicates the importance of deubiquitination enzymes (DUBs) in innate immunity, it is unknown if they participate in A3G stability. Here, we found that USP49 directly interacts with A3G and efficiently removes ubiquitin, consequently increasing A3G protein expression and significantly enhancing its anti-HIV-1 activity. Unexpectedly, A3G degradation was also mediated by a Vif- and cullin-ring-independent pathway, which was effectively counteracted by USP49. Furthermore, clinical data suggested that USP49 is correlated with A3G protein expression and hypermutations in Vif-positive proviruses, and inversely with the intact provirus ratio in the HIV-1 latent reservoir. Our studies demonstrated a mechanism to effectively stabilize A3G expression, which could comprise a target to control HIV-1 infection and eradicate the latent reservoir. |
| first_indexed | 2024-04-11T09:18:44Z |
| format | Article |
| id | doaj.art-edd1ce580637416ab763804a828140ed |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:18:44Z |
| publishDate | 2019-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-edd1ce580637416ab763804a828140ed2022-12-22T04:32:16ZengeLife Sciences Publications LtdeLife2050-084X2019-08-01810.7554/eLife.48318USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replicationTing Pan0https://orcid.org/0000-0002-7106-7312Zheng Song1Liyang Wu2Guangyan Liu3https://orcid.org/0000-0002-5891-1830Xiancai Ma4https://orcid.org/0000-0002-4934-4221Zhilin Peng5Mo Zhou6Liting Liang7Bingfeng Liu8Jun Liu9Junsong Zhang10Xuanhong Zhang11Ryan Huang12Jiacong Zhao13Yonghong Li14Xuemei Ling15Yuewen Luo16Xiaoping Tang17Weiping Cai18Kai Deng19Linghua Li20Hui Zhang21https://orcid.org/0000-0003-3620-610XInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInfectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaInfectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInfectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaInfectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaInfectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaThe antiviral activity of host factor apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G, A3G) and its degradation mediated by human immunodeficiency virus type 1 (HIV-1) Vif protein are important topics. Although accumulating evidence indicates the importance of deubiquitination enzymes (DUBs) in innate immunity, it is unknown if they participate in A3G stability. Here, we found that USP49 directly interacts with A3G and efficiently removes ubiquitin, consequently increasing A3G protein expression and significantly enhancing its anti-HIV-1 activity. Unexpectedly, A3G degradation was also mediated by a Vif- and cullin-ring-independent pathway, which was effectively counteracted by USP49. Furthermore, clinical data suggested that USP49 is correlated with A3G protein expression and hypermutations in Vif-positive proviruses, and inversely with the intact provirus ratio in the HIV-1 latent reservoir. Our studies demonstrated a mechanism to effectively stabilize A3G expression, which could comprise a target to control HIV-1 infection and eradicate the latent reservoir.https://elifesciences.org/articles/48318USP49HIV-1APOBEC3GVifdeubiquitination |
| spellingShingle | Ting Pan Zheng Song Liyang Wu Guangyan Liu Xiancai Ma Zhilin Peng Mo Zhou Liting Liang Bingfeng Liu Jun Liu Junsong Zhang Xuanhong Zhang Ryan Huang Jiacong Zhao Yonghong Li Xuemei Ling Yuewen Luo Xiaoping Tang Weiping Cai Kai Deng Linghua Li Hui Zhang USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication eLife USP49 HIV-1 APOBEC3G Vif deubiquitination |
| title | USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication |
| title_full | USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication |
| title_fullStr | USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication |
| title_full_unstemmed | USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication |
| title_short | USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication |
| title_sort | usp49 potently stabilizes apobec3g protein by removing ubiquitin and inhibits hiv 1 replication |
| topic | USP49 HIV-1 APOBEC3G Vif deubiquitination |
| url | https://elifesciences.org/articles/48318 |
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