Journal
SCIENTIFIC REPORTS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-022-11181-0
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Funding
- Health Department of the Catalan Government/Generalitat de Catalunya
- ISCIII
- Instituto de Salud Carlos III, Fondo de Investigacion Sanitaria (FIS) - FEDER [PI12/02408, PI15/01053]
- Grifols
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This study evaluated the interrelationship between HIV and autophagy using human ex vivo lymphoid tissue cultures as an HIV infection model. The results showed that HIV infection increased autophagy, and both enhancing and blocking autophagy could decrease HIV replication. Therefore, targeting the autophagic pathway could be a new therapeutic approach to treat HIV-1 infection. Ex vivo cultures of human lymphoid tissue are a suitable model to obtain further insights into the intricate relationship between HIV and autophagy.
A complex link exists between HIV-1 and autophagy, and discordant results have been reported in different in vitro models regarding the way HIV and autophagy modulate each other. Despite this, there is very limited knowledge about the interplay between HIV and autophagy in vivo in lymphoid tissue, due in part by the lack of cell models that recapitulate the in vivo setting. Here, we evaluate the interrelationship between HIV and autophagy using human ex vivo lymphoid tissue cultures as an HIV infection model. Our results showed that human lymphoid aggregated cultures (HLACs) from tonsillar tissue displayed fully functional autophagic activity. In this system, HIV infection resulted in an increase in autophagy. Notably, we observed that both, autophagy-enhancing (rapamycin) or blocking drugs (3-methyladenine, chloroquine and bafilomycin), were able to decrease HIV-DNA levels and HIV replication. Therefore, efficient HIV-1 replication requires a fine-tuned level of autophagy, so modifications of this balance will have a negative impact on its replication. Therefore, targeting the autophagic pathway could be a new therapeutic approach to be explored to treat HIV-1 infection. Ex vivo cultures of human lymphoid tissue are a suitable model to obtain further insights into HIV and its intricate relationship with autophagy.
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