Rôle et ciblage de l’intégrine α4β7 dans la physiopathologie des MICI et de l’infection par le VIH

Girard, Alexandre; Rochereau, Nicolas; Roblin, Xavier; Genin, Christian; Paul, Stéphane

doi:10.1051/medsci/20153110016

Cited by 3 publications

(2 citation statements)

References 41 publications

(25 reference statements)

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“…In particular, it is well known that adhesion molecules expressed at the cell surface, such as integrins, are the first cellular components that interact with incoming pathogens. The role of these proteins has been largely studied in the context of HIV-1 infection and are known to facilitate the recognition between HIV-1 Env and its specific receptors (43)(44)(45)(46). It is worth noting that a recent study has shown that integrins harbor a LIR motif (LC3-Interacting Region) in their cytoplasmic part (47).…”

Section: Discussionmentioning

confidence: 99%

LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4+ T lymphocytes

Pradel

Deffieu

Robert-Hebmann

et al. 2023

Preprint

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HIV-1 entry into CD4+ T lymphocytes relies on the viral and cellular membranes fusion, leading to viral capsid delivery in the cytoplasm of target cells. The conjugation of ATG8/LC3B protein, process referred to as ATG8ylation and mainly studied in the context of autophagy, occurs transiently in the early stages of the HIV-1 replication cycle in CD4+ T lymphocytes. Despite numerous studies investigating the interplays of HIV-1 with autophagy machinery, the impact of ATG8ylation in the early stages of HIV-1 infection remains unknown. Here we found that HIV-1 exposure leads to the rapid enrichment of LC3B towards the target cell plasma membrane, in close proximity with the incoming viral particles. Furthermore, we demonstrated that ATG8ylation is a key event that facilitates HIV-1 fusion with target CD4+ T cells. Interestingly, this effect is independent of the canonical autophagy pathway as ATG13 silencing does not prevent HIV-1 entry. Together, our results provide an unconventional role of LC3B conjugation subverted by HIV-1 to achieve a critical early step of its replication cycle.

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Section: Discussionmentioning

confidence: 99%

LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4+ T lymphocytes

Pradel

Deffieu

Robert-Hebmann

et al. 2023

Preprint

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“…Arthos et al ont montré que la protéine d'enveloppe virale gp120 était capable de se fixer sur la forme activée de l'intégrine 4 7, facilitant ainsi l'infection lymphocytaire via l'activation d'une autre intégrine et la formation d'une synapse virologique [18]. L'intégrine 4 7 joue donc un rôle majeur dans l'infection virale et la déplétion des lymphocytes muqueux [20,62] (➜). Les lymphocytes Th17 sont une sous-population de lymphocytes T CD4 + particulièrement impliqués dans l'immunité muqueuse.…”

Section: Le Galt Premier Réservoir Et Sanctuaire Anatomique Pour Le unclassified

Infection par le virus de l’immunodéficience humaine

et al. 2015

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An integrated QSAR modeling approach to explore the structure–property and selectivity relationships of N-benzoyl-l-biphenylalanines as integrin antagonists

et al. 2017

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Integrins [Formula: see text] and [Formula: see text] are important targets to treat different inflammatory diseases, such as multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, atherosclerosis, and asthma. Despite being valuable targets, only a few work has been reported to date regarding molecular modeling studies on these integrins. Not only that, none of these reports addressed the selectivity issue between integrins [Formula: see text] and [Formula: see text]. Therefore, a major challenge regarding the design and discovery of selective integrin antagonists remains. In this study, a series of 142 N-benzoyl-L-biphenylalanines having both integrin [Formula: see text] and [Formula: see text] inhibitory activities were considered for a variety of QSAR approaches including regression and classification-based 2D-QSARs, Hologram QSARs, 3D-QSAR CoMFA and CoMSIA studies to identify the structural requirements of these integrin antagonists. All these QSAR models were statistically validated and subsequently correlated with each other to get a detailed understanding of the activity and selectivity profiles of these molecules.

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Rôle et ciblage de l’intégrine α4β7 dans la physiopathologie des MICI et de l’infection par le VIH

Cited by 3 publications

References 41 publications

LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4+ T lymphocytes

LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4+ T lymphocytes

Infection par le virus de l’immunodéficience humaine

An integrated QSAR modeling approach to explore the structure–property and selectivity relationships of N-benzoyl-l-biphenylalanines as integrin antagonists

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