Entry, replication and innate immunity evasion of BANAL-236, a SARS-CoV-2-related bat virus, in Rhinolophus and human cells
Rattachement africain : fr, us, es, de. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Abstract Asian Rhinolophus bats are considered the natural reservoirs of an ancestral SARS-CoV-2. However, the biology of SARS-CoV-2-related viruses in bat cells is not well understood. Here, we investigated the replication of BANAL-236, the only bat-derived SARS-CoV-2 relative isolated to date, in Rhinolophus cells. BANAL-236 did not replicate in wild-type Rhinolophus cell lines. Entry assays using pseudoviruses expressing the spike proteins (S) of SARS-CoV-2, BANAL-236, and BANAL-52 revealed that efficient S-mediated entry depends on the expression of human ACE2 (hACE2) and human TMPRSS2 (hTMPRSS2) in human and Rhinolophus cells. Expression of Rhinolophus entry factors, either alone or in combination, did not facilitate SARS-CoV-2 or BANAL-236 entry in human cells, suggesting that the S protein of BANAL-236 interacts more efficiently with hACE2 than with its Rhinolophus counterpart (rACE2). Through biochemical, virological, and electron microscopy analyses, we showed that BANAL-236 and SARS-CoV-2 completed their replication cycles in a Rhinolophus cell line engineered to express high levels of hACE2 and hTMPRSS2. Despite efficient viral replication in modified Rhinolophus and human cells, no induction of interferon (IFN)-stimulated genes was detected. Using a screening approach, we identified several BANAL-236 proteins that antagonize IFN production and signaling in human cells. Our findings thus show that BANAL-236 possesses critical features that enabled zoonotic spillover: hACE2 usage and potent evasion of human IFN responses. The Rhinolophus cellular model we established offers a platform for further investigating the interactions between bat coronaviruses and their reservoir hosts. Author summary Bats are known reservoirs for viruses that cause severe diseases in humans, such as coronaviruses and filoviruses. Bat species naturally or experimentally infected with these viruses rarely exhibit clinical symptoms, suggesting an evolved tolerance to viral infections. To elucidate the mechanisms underlying viral tolerance and to identify factors that could facilitate zoonotic spillover, it is essential to study the replication of bat-borne viruses in relevant bat cellular models. Here, we investigated the replication of BANAL-236, a SARS-CoV-2 related virus isolated from fecal samples of Rhinolophus bats in Northen Laos, in a novel cell line derived from Rhinolophus ferrumequinum lung fibroblasts. Our findings reveal that BANAL-236 can efficiently use human entry factors and potently evade the human innate immune response, two traits that may have contributed to its zoonotic transmission. Furthermore, the R. ferrumequinum cell lines we developed is a valuable model for investigating the molecular interactions between sarbecoviruses and their natural hosts.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Entry, replication and innate immunity evasion of BANAL-236, a SARS-CoV-2-related bat virus, in Rhinolophus and human cells
- Date Crossref
- 20/04/2026
- Éditeur
- Public Library of Science (PLoS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Centre National de la Recherche Scientifique pays non établi dans la noticeOrganisme public
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Institut Pasteur pays non établi dans la noticeOrganisation à but non lucratif
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Université Paris Cité Institut Pasteur pays non établi dans la noticeUniversité ou école supérieure
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Department of Virology pays non établi dans la noticeStructure de recherche
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Icahn School of Medicine at Mount Sinai Department of Microbiology pays non établi dans la noticeUniversité ou école supérieure
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Estación Biológica de Doñana pays non établi dans la noticeStructure de recherche
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Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública pays non établi dans la noticeStructure de recherche
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Commissariat à l'Énergie Atomique et aux Énergies Alternatives pays non établi dans la noticeOrganisme public
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Université Paris-Saclay Département Médicaments et Technologies pour la Santé (DMTS) pays non établi dans la noticeUniversité ou école supérieure
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CEA Paris-Saclay pays non établi dans la noticeOrganisme public
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Institut de Biologie et Technologies pays non établi dans la noticeStructure de recherche
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Médicaments et Technologies pour la Santé pays non établi dans la noticeStructure de recherche
Centre National de la Recherche Scientifique, Institut Pasteur et Institut Pasteur — Université Paris Cité, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.