Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells

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  • dc.contributor.author Kobayashi-Ishihara, Mie
  • dc.contributor.author Smutná, Katarína, 1991-
  • dc.contributor.author Alonso, Florencia E.
  • dc.contributor.author Argilaguet Marqués, Jordi, 1977-
  • dc.contributor.author Esteve-Codina, Anna
  • dc.contributor.author Geiger, Kerstin
  • dc.contributor.author Rogenmoser, Selina
  • dc.contributor.author Oliva Miguel, Baldomero
  • dc.contributor.author Martinez, Javier P.
  • dc.contributor.author Díez Antón, Juana, 1962-
  • dc.contributor.author Meyerhans, Andreas
  • dc.date.accessioned 2023-06-12T06:32:20Z
  • dc.date.available 2023-06-12T06:32:20Z
  • dc.date.issued 2023
  • dc.description.abstract Latency is a major barrier towards virus elimination in HIV-1-infected individuals. Yet, the mechanisms that contribute to the maintenance of HIV-1 latency are incompletely understood. Here we describe the Schlafen 12 protein (SLFN12) as an HIV-1 restriction factor that establishes a post-transcriptional block in HIV-1-infected cells and thereby inhibits HIV-1 replication and virus reactivation from latently infected cells. The inhibitory activity is dependent on the HIV-1 codon usage and on the SLFN12 RNase active sites. Within HIV-1-infected individuals, SLFN12 expression in PBMCs correlated with HIV-1 plasma viral loads and proviral loads suggesting a link with the general activation of the immune system. Using an RNA FISH-Flow HIV-1 reactivation assay, we demonstrate that SLFN12 expression is enriched in infected cells positive for HIV-1 transcripts but negative for HIV-1 proteins. Thus, codon-usage dependent translation inhibition of HIV-1 proteins participates in HIV-1 latency and can restrict the amount of virus release after latency reversal.
  • dc.description.sponsorship This work was supported by following grants: M.K.I., JSPS Oversea Research Fellowship and Takeda Science Foundation; A.E.C., PT17/0009/0019 (ISCIII/MINECO and FEDER); M.J.B., RTI2018-101082-B-I00 and PID2021-123321OB-I00 [MINECO/FEDER]), and the Miguel Servet program by ISCIII (CP17/00179 and CPII22/00005); C.B., M.R.R., C.D.C., European Union’s Horizon 2020 research and innovation program under grant agreement 681137-EAVI2020 and NIH grant P01-AI131568; J.D., the Spanish Ministry of Science and Innovation (PID2019106959RB-I00/AEI/10.13039/501100011033); A.M., the Spanish Ministry of Science and Innovation (PID2019-106323RB-I00 AEI//10.13039/501100011033) and the institutional “María de Maeztu” Programme for Units of Excellence in R&D (CEX2018-000792-M).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Kobayashi-Ishihara M, Frazão Smutná K, Alonso FE, Argilaguet J, Esteve-Codina A, Geiger K, et al. Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells. Commun Biol. 2023 May 10;6(1):487. DOI: 10.1038/s42003-023-04841-y
  • dc.identifier.doi http://dx.doi.org/10.1038/s42003-023-04841-y
  • dc.identifier.issn 2399-3642
  • dc.identifier.uri http://hdl.handle.net/10230/57154
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Commun Biol. 2023 May 10;6(1):487
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/681137
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-101082-B-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-123321OB-I00
  • dc.rights © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword HIV infections
  • dc.subject.keyword Restriction factors
  • dc.title Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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