Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo

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, d...

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Authors: Pedreño-López, Sònia|||0000-0002-1919-3530, García Rodríguez, Elisabet, Guerrero, Dolores, Gomez, Elisabet|||0000-0002-9779-5940, Molina Mateu, Laura, Orera Pérez, Fernando, Senserrich, Jordi|||0000-0002-8021-1718, Clotet Sala, Bonaventura|||0000-0003-3232-4598, Cabrera Navarro, Cecilia|||0000-0002-9941-6828
Format: article
Publication Date:2022
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:282866
Online Access:https://ddd.uab.cat/record/282866
https://dx.doi.org/urn:doi:10.1038/s41598-022-11181-0
Access Level:Open access
Keyword:HIV infections
Macroautophagy
Description
Summary: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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