ArticlePLoS pathogens2024
HIV-1 exploits LBPA-dependent intraepithelial trafficking for productive infection of human intestinal mucosa.
Article in PLoS pathogens, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Protocol for a primary human 2D intestinal epithelium-dendritic cell co-culture organoid model to study mucosal immunity and viral infections.STAR protocols · 2026Article
- Organoids: From Bench to Bedside Applications.MedComm · 2026Review
- Organoids: technology refining, current applications and future directions.Molecular biomedicine · 2026Review
- Lipid nanoparticle-based mRNA platforms for mucosal HIV vaccines: formulation advances, immune mechanisms, and translational pathways.Archives of microbiology · 2025Review
- Autophagy-enhancing strategies to promote intestinal viral resistance and mucosal barrier function in SARS-CoV-2 infection.Autophagy reports · 2025Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The gastrointestinal tract is a prominent portal of entry for HIV-1 during sexual or perinatal transmission, as well as a major site of HIV-1 persistence and replication. Elucidation of underlying mechanisms of intestinal HIV-1 infection are thus needed for the advancement of HIV-1 curative therapies. Here, we present a human 2D intestinal immuno-organoid system to model HIV-1 disease that recapitulates tissue compartmentalization and epithelial-immune cellular interactions. Our data demonstrate that apical exposure of intestinal epithelium to HIV-1 results in viral internalization, with subsequent basolateral shedding of replication-competent viruses, in a manner that is impervious to antiretroviral treatment. Incorporation of subepithelial dendritic cells resulted in HIV-1 luminal sampling and amplification of residual viral replication of lab-adapted and transmitted-founder (T/F) HIV-1 variants. Markedly, intraepithelial viral capture ensued an altered distribution of specialized endosomal pathways alongside durable sequestration of infectious HIV-1 within lysobisphosphatidic acid (LPBA)-rich vesicles. Therapeutic neutralization of LBPA-dependent trafficking limited productive HIV-1 infection, and thereby demonstrated the pivotal role of intraepithelial multivesicular endosomes as niches for virulent HIV-1 within the intestinal mucosa. Our study showcases the application of primary human 2D immune-competent organoid cultures in uncovering mechanisms of intestinal HIV-1 disease as well as a platform for preclinical antiviral drug discovery.
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