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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156091/ https://www.ncbi.nlm.nih.gov/pubmed/34069225 http://dx.doi.org/10.3390/cells10051207 |
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author | Ciccosanti, Fabiola Corazzari, Marco Casetti, Rita Amendola, Alessandra Collalto, Diletta Refolo, Giulia Vergori, Alessandra Taibi, Chiara D’Offizi, Gianpiero Antinori, Andrea Agrati, Chiara Fimia, Gian Maria Ippolito, Giuseppe Piacentini, Mauro Nardacci, Roberta |
author_facet | Ciccosanti, Fabiola Corazzari, Marco Casetti, Rita Amendola, Alessandra Collalto, Diletta Refolo, Giulia Vergori, Alessandra Taibi, Chiara D’Offizi, Gianpiero Antinori, Andrea Agrati, Chiara Fimia, Gian Maria Ippolito, Giuseppe Piacentini, Mauro Nardacci, Roberta |
author_sort | Ciccosanti, Fabiola |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8156091 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81560912021-05-28 High Levels of TRIM5α Are Associated with Xenophagy in HIV-1-Infected Long-Term Nonprogressors Ciccosanti, Fabiola Corazzari, Marco Casetti, Rita Amendola, Alessandra Collalto, Diletta Refolo, Giulia Vergori, Alessandra Taibi, Chiara D’Offizi, Gianpiero Antinori, Andrea Agrati, Chiara Fimia, Gian Maria Ippolito, Giuseppe Piacentini, Mauro Nardacci, Roberta Cells Article 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. MDPI 2021-05-14 /pmc/articles/PMC8156091/ /pubmed/34069225 http://dx.doi.org/10.3390/cells10051207 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ciccosanti, Fabiola Corazzari, Marco Casetti, Rita Amendola, Alessandra Collalto, Diletta Refolo, Giulia Vergori, Alessandra Taibi, Chiara D’Offizi, Gianpiero Antinori, Andrea Agrati, Chiara Fimia, Gian Maria Ippolito, Giuseppe Piacentini, Mauro Nardacci, Roberta High Levels of TRIM5α Are Associated with Xenophagy in HIV-1-Infected Long-Term Nonprogressors |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156091/ https://www.ncbi.nlm.nih.gov/pubmed/34069225 http://dx.doi.org/10.3390/cells10051207 |
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