High Levels of TRIM5α Are Associated with Xenophagy in HIV-1-Infected Long-Term Nonprogressors
Autophagy is a lysosomal-dependent degradative mechanism essential in maintaining cellular homeostasis, but it is also considered an ancient form of innate eukaryotic fighting against invading microorganisms. Mounting evidence has shown that HIV-1 is a critical target of autophagy that plays a role...
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MDPI AG
2021-05-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/5/1207 |
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| author | Fabiola Ciccosanti Marco Corazzari Rita Casetti Alessandra Amendola Diletta Collalto Giulia Refolo Alessandra Vergori Chiara Taibi Gianpiero D’Offizi Andrea Antinori Chiara Agrati Gian Maria Fimia Giuseppe Ippolito Mauro Piacentini Roberta Nardacci |
| author_facet | Fabiola Ciccosanti Marco Corazzari Rita Casetti Alessandra Amendola Diletta Collalto Giulia Refolo Alessandra Vergori Chiara Taibi Gianpiero D’Offizi Andrea Antinori Chiara Agrati Gian Maria Fimia Giuseppe Ippolito Mauro Piacentini Roberta Nardacci |
| author_sort | Fabiola Ciccosanti |
| collection | DOAJ |
| description | Autophagy is a lysosomal-dependent degradative mechanism essential in maintaining cellular homeostasis, but it is also considered an ancient form of innate eukaryotic fighting against invading microorganisms. Mounting evidence has shown that HIV-1 is a critical target of autophagy that plays a role in HIV-1 replication and disease progression. In a special subset of HIV-1-infected patients that spontaneously and durably maintain extremely low viral replication, namely, long-term nonprogressors (LTNP), the resistance to HIV-1-induced pathogenesis is accompanied, in vivo, by a significant increase in the autophagic activity in peripheral blood mononuclear cells. Recently, a new player in the battle of autophagy against HIV-1 has been identified, namely, tripartite motif protein 5α (TRIM5α). In vitro data demonstrated that TRIM5α directly recognizes HIV-1 and targets it for autophagic destruction, thus protecting cells against HIV-1 infection. In this paper, we analyzed the involvement of this factor in the control of HIV-1 infection through autophagy, in vivo, in LTNP. The results obtained showed significantly higher levels of TRIM5α expression in cells from LTNP with respect to HIV-1-infected normal progressor patients. Interestingly, the colocalization of TRIM5α and HIV-1 proteins in autophagic vacuoles in LTNP cells suggested the participation of TRIM5α in the autophagy containment of HIV-1 in LTNP. Altogether, our results point to a protective role of TRIM5α in the successful control of the chronic viral infection in HIV-1-controllers through the autophagy mechanism. In our opinion, these findings could be relevant in fighting against HIV-1 disease, because autophagy inducers might be employed in combination with antiretroviral drugs. |
| first_indexed | 2024-03-10T11:23:39Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T11:23:39Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-24a376728fb6434da3ff91336757b53b2023-11-21T19:49:09ZengMDPI AGCells2073-44092021-05-01105120710.3390/cells10051207High Levels of TRIM5α Are Associated with Xenophagy in HIV-1-Infected Long-Term NonprogressorsFabiola Ciccosanti0Marco Corazzari1Rita Casetti2Alessandra Amendola3Diletta Collalto4Giulia Refolo5Alessandra Vergori6Chiara Taibi7Gianpiero D’Offizi8Andrea Antinori9Chiara Agrati10Gian Maria Fimia11Giuseppe Ippolito12Mauro Piacentini13Roberta Nardacci14Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyClinical Department, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyClinical Department, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyClinical Department, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyClinical Department, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, 00149 Rome, ItalyAutophagy is a lysosomal-dependent degradative mechanism essential in maintaining cellular homeostasis, but it is also considered an ancient form of innate eukaryotic fighting against invading microorganisms. Mounting evidence has shown that HIV-1 is a critical target of autophagy that plays a role in HIV-1 replication and disease progression. In a special subset of HIV-1-infected patients that spontaneously and durably maintain extremely low viral replication, namely, long-term nonprogressors (LTNP), the resistance to HIV-1-induced pathogenesis is accompanied, in vivo, by a significant increase in the autophagic activity in peripheral blood mononuclear cells. Recently, a new player in the battle of autophagy against HIV-1 has been identified, namely, tripartite motif protein 5α (TRIM5α). In vitro data demonstrated that TRIM5α directly recognizes HIV-1 and targets it for autophagic destruction, thus protecting cells against HIV-1 infection. In this paper, we analyzed the involvement of this factor in the control of HIV-1 infection through autophagy, in vivo, in LTNP. The results obtained showed significantly higher levels of TRIM5α expression in cells from LTNP with respect to HIV-1-infected normal progressor patients. Interestingly, the colocalization of TRIM5α and HIV-1 proteins in autophagic vacuoles in LTNP cells suggested the participation of TRIM5α in the autophagy containment of HIV-1 in LTNP. Altogether, our results point to a protective role of TRIM5α in the successful control of the chronic viral infection in HIV-1-controllers through the autophagy mechanism. In our opinion, these findings could be relevant in fighting against HIV-1 disease, because autophagy inducers might be employed in combination with antiretroviral drugs.https://www.mdpi.com/2073-4409/10/5/1207autophagyTRIM5αHIV-1long-term nonprogressorsxenophagy |
| spellingShingle | Fabiola Ciccosanti Marco Corazzari Rita Casetti Alessandra Amendola Diletta Collalto Giulia Refolo Alessandra Vergori Chiara Taibi Gianpiero D’Offizi Andrea Antinori Chiara Agrati Gian Maria Fimia Giuseppe Ippolito Mauro Piacentini Roberta Nardacci High Levels of TRIM5α Are Associated with Xenophagy in HIV-1-Infected Long-Term Nonprogressors Cells autophagy TRIM5α HIV-1 long-term nonprogressors xenophagy |
| title | High Levels of TRIM5α Are Associated with Xenophagy in HIV-1-Infected Long-Term Nonprogressors |
| title_full | High Levels of TRIM5α Are Associated with Xenophagy in HIV-1-Infected Long-Term Nonprogressors |
| title_fullStr | High Levels of TRIM5α Are Associated with Xenophagy in HIV-1-Infected Long-Term Nonprogressors |
| title_full_unstemmed | High Levels of TRIM5α Are Associated with Xenophagy in HIV-1-Infected Long-Term Nonprogressors |
| title_short | High Levels of TRIM5α Are Associated with Xenophagy in HIV-1-Infected Long-Term Nonprogressors |
| title_sort | high levels of trim5α are associated with xenophagy in hiv 1 infected long term nonprogressors |
| topic | autophagy TRIM5α HIV-1 long-term nonprogressors xenophagy |
| url | https://www.mdpi.com/2073-4409/10/5/1207 |
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