Retroviral foamy virus gag induces parkin-dependent mitophagy
Abstract Background Prototype foamy virus (PFV) is a complex retrovirus that can maintain latent infection for life after viral infection of the host. However, the mechanism of latent infection with PFV remains unclear. Our previous studies have shown that PFV promotes autophagy flux, but whether PF...
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BMC
2025-05-01
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| Series: | Retrovirology |
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| Online Access: | https://doi.org/10.1186/s12977-025-00664-3 |
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| author | Shanshan Wang Tongtong Du Jun Yan Yingcheng Zheng Yinglian Tang Juejie Wu Qian Xu Shanshan Xu Luo Liu Xiong Chen Song Han Jun Yin Biwen Peng Xiaohua He Wanhong Liu |
| author_facet | Shanshan Wang Tongtong Du Jun Yan Yingcheng Zheng Yinglian Tang Juejie Wu Qian Xu Shanshan Xu Luo Liu Xiong Chen Song Han Jun Yin Biwen Peng Xiaohua He Wanhong Liu |
| author_sort | Shanshan Wang |
| collection | DOAJ |
| description | Abstract Background Prototype foamy virus (PFV) is a complex retrovirus that can maintain latent infection for life after viral infection of the host. However, the mechanism of latent infection with PFV remains unclear. Our previous studies have shown that PFV promotes autophagy flux, but whether PFV causes mitophagy remains unclear. Results In this study, we demonstrated that PFV infection damages mitochondria, increases mitochondria reactive oxygen species (mtROS) production, and induces mitophagy in a time-dependent manner. Further investigation revealed that PFV Gag is a crucial protein responsible for triggering mitophagy. The overexpression of Gag leads to mitochondrial damage and stimulates mitophagy in a dose-dependent manner. Additionally, overexpression of Gag activates the PINK1-Parkin signaling pathway, while the knockdown of Parkin inhibits Gag-induced mitophagy. Furthermore, Rab5a was significantly upregulated in cells overexpressed Gag, and the inhibition of Rab5a reversed the effects of Gag-induced mitophagy. Conclusions Our data suggested that PFV can induce mitophagy and Gag induces Parkin-dependent mitophagy by upregulating Rab5a. These findings not only enhance a better understanding of the foamy virus infection mechanisms but also provide critical insights into novel virus-host cell interactions. |
| format | Article |
| id | doaj-art-fdc290aed32842b39628a0a4aaf6cd9e |
| institution | DOAJ |
| issn | 1742-4690 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj-art-fdc290aed32842b39628a0a4aaf6cd9e2025-08-20T02:55:32ZengBMCRetrovirology1742-46902025-05-0122111310.1186/s12977-025-00664-3Retroviral foamy virus gag induces parkin-dependent mitophagyShanshan Wang0Tongtong Du1Jun Yan2Yingcheng Zheng3Yinglian Tang4Juejie Wu5Qian Xu6Shanshan Xu7Luo Liu8Xiong Chen9Song Han10Jun Yin11Biwen Peng12Xiaohua He13Wanhong Liu14Hubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityHubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityDepartment of Laboratory Medicine, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and TechnologyHubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityHubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityHubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityHubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityDepartment of Allergy, Zhongnan Hospital of Wuhan, UniversityBeijing Bioprocess Key Laboratory, Beijing University of Chemical TechnologyKey Laboratory of Environmental Pollution Monitoring and Disease Control(Guizhou Medical University), Ministry of EducationHubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityHubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityHubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityHubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityHubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityAbstract Background Prototype foamy virus (PFV) is a complex retrovirus that can maintain latent infection for life after viral infection of the host. However, the mechanism of latent infection with PFV remains unclear. Our previous studies have shown that PFV promotes autophagy flux, but whether PFV causes mitophagy remains unclear. Results In this study, we demonstrated that PFV infection damages mitochondria, increases mitochondria reactive oxygen species (mtROS) production, and induces mitophagy in a time-dependent manner. Further investigation revealed that PFV Gag is a crucial protein responsible for triggering mitophagy. The overexpression of Gag leads to mitochondrial damage and stimulates mitophagy in a dose-dependent manner. Additionally, overexpression of Gag activates the PINK1-Parkin signaling pathway, while the knockdown of Parkin inhibits Gag-induced mitophagy. Furthermore, Rab5a was significantly upregulated in cells overexpressed Gag, and the inhibition of Rab5a reversed the effects of Gag-induced mitophagy. Conclusions Our data suggested that PFV can induce mitophagy and Gag induces Parkin-dependent mitophagy by upregulating Rab5a. These findings not only enhance a better understanding of the foamy virus infection mechanisms but also provide critical insights into novel virus-host cell interactions.https://doi.org/10.1186/s12977-025-00664-3Prototype foamy virusGagMitophagyParkinRab5a |
| spellingShingle | Shanshan Wang Tongtong Du Jun Yan Yingcheng Zheng Yinglian Tang Juejie Wu Qian Xu Shanshan Xu Luo Liu Xiong Chen Song Han Jun Yin Biwen Peng Xiaohua He Wanhong Liu Retroviral foamy virus gag induces parkin-dependent mitophagy Retrovirology Prototype foamy virus Gag Mitophagy Parkin Rab5a |
| title | Retroviral foamy virus gag induces parkin-dependent mitophagy |
| title_full | Retroviral foamy virus gag induces parkin-dependent mitophagy |
| title_fullStr | Retroviral foamy virus gag induces parkin-dependent mitophagy |
| title_full_unstemmed | Retroviral foamy virus gag induces parkin-dependent mitophagy |
| title_short | Retroviral foamy virus gag induces parkin-dependent mitophagy |
| title_sort | retroviral foamy virus gag induces parkin dependent mitophagy |
| topic | Prototype foamy virus Gag Mitophagy Parkin Rab5a |
| url | https://doi.org/10.1186/s12977-025-00664-3 |
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