Targeting autophagy to treat HIV immune dysfunction
Chronic immune activation and inflammation are hallmarks of Human Immunodeficiency Virus-1 (HIV-1) pathogenesis. Therefore, approaches to safely reduce systematic inflammation are essential to improve immune responses and thus slow or prevent HIV progression. Autophagy is a cellular mechanism for th...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Autophagy Reports |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/27694127.2023.2254615 |
| _version_ | 1797685708399312896 |
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| author | Wenli Mu Heather Martin Anjie Zhen |
| author_facet | Wenli Mu Heather Martin Anjie Zhen |
| author_sort | Wenli Mu |
| collection | DOAJ |
| description | Chronic immune activation and inflammation are hallmarks of Human Immunodeficiency Virus-1 (HIV-1) pathogenesis. Therefore, approaches to safely reduce systematic inflammation are essential to improve immune responses and thus slow or prevent HIV progression. Autophagy is a cellular mechanism for the disposal of damaged organelles and elimination of intracellular pathogens. It is not only vital for energy homeostasis, but also plays a critical role in regulating immunity. However, how it regulates inflammation and antiviral T cell responses during HIV infection is unclear. Our study demonstrated that impairment of autophagy leads to spontaneous type I-Interferons (IFN-I) signaling, while autophagy induction reduces IFN-I signaling in macrophages. Importantly, we demonstrated that in vivo treatment of autophagy inducer rapamycin in chronically HIV infected humanized mice decreased chronic IFN-I signaling, improved exhausted anti-viral T cell function, and reduced viral loads. Taken together, our study supports the therapeutic potential of rapamycin and potentially other autophagy inducers in alleviating HIV-1 immunopathogenesis and improving anti-viral T cell responses. |
| first_indexed | 2024-03-12T00:55:12Z |
| format | Article |
| id | doaj.art-7379fbd278a94e2c8f4709f4f4798e74 |
| institution | Directory Open Access Journal |
| issn | 2769-4127 |
| language | English |
| last_indexed | 2024-03-12T00:55:12Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj.art-7379fbd278a94e2c8f4709f4f4798e742023-09-14T13:24:41ZengTaylor & Francis GroupAutophagy Reports2769-41272023-12-012110.1080/27694127.2023.22546152254615Targeting autophagy to treat HIV immune dysfunctionWenli Mu0Heather Martin1Anjie Zhen2David Geffen School of Medicine at UCLADavid Geffen School of Medicine at UCLADavid Geffen School of Medicine at UCLAChronic immune activation and inflammation are hallmarks of Human Immunodeficiency Virus-1 (HIV-1) pathogenesis. Therefore, approaches to safely reduce systematic inflammation are essential to improve immune responses and thus slow or prevent HIV progression. Autophagy is a cellular mechanism for the disposal of damaged organelles and elimination of intracellular pathogens. It is not only vital for energy homeostasis, but also plays a critical role in regulating immunity. However, how it regulates inflammation and antiviral T cell responses during HIV infection is unclear. Our study demonstrated that impairment of autophagy leads to spontaneous type I-Interferons (IFN-I) signaling, while autophagy induction reduces IFN-I signaling in macrophages. Importantly, we demonstrated that in vivo treatment of autophagy inducer rapamycin in chronically HIV infected humanized mice decreased chronic IFN-I signaling, improved exhausted anti-viral T cell function, and reduced viral loads. Taken together, our study supports the therapeutic potential of rapamycin and potentially other autophagy inducers in alleviating HIV-1 immunopathogenesis and improving anti-viral T cell responses.http://dx.doi.org/10.1080/27694127.2023.2254615ant-hiv-1 immunityautophagyhiv-1 immunopathogenesisifn-i signalinginflammationrapamycinimmune exhaustion |
| spellingShingle | Wenli Mu Heather Martin Anjie Zhen Targeting autophagy to treat HIV immune dysfunction Autophagy Reports ant-hiv-1 immunity autophagy hiv-1 immunopathogenesis ifn-i signaling inflammation rapamycin immune exhaustion |
| title | Targeting autophagy to treat HIV immune dysfunction |
| title_full | Targeting autophagy to treat HIV immune dysfunction |
| title_fullStr | Targeting autophagy to treat HIV immune dysfunction |
| title_full_unstemmed | Targeting autophagy to treat HIV immune dysfunction |
| title_short | Targeting autophagy to treat HIV immune dysfunction |
| title_sort | targeting autophagy to treat hiv immune dysfunction |
| topic | ant-hiv-1 immunity autophagy hiv-1 immunopathogenesis ifn-i signaling inflammation rapamycin immune exhaustion |
| url | http://dx.doi.org/10.1080/27694127.2023.2254615 |
| work_keys_str_mv | AT wenlimu targetingautophagytotreathivimmunedysfunction AT heathermartin targetingautophagytotreathivimmunedysfunction AT anjiezhen targetingautophagytotreathivimmunedysfunction |