1. Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells.
- Author
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Kobayashi-Ishihara, Mie, Frazão Smutná, Katarína, Alonso, Florencia E., Argilaguet, Jordi, Esteve-Codina, Anna, Geiger, Kerstin, Genescà, Meritxell, Grau-Expósito, Judith, Duran-Castells, Clara, Rogenmoser, Selina, Böttcher, René, Jungfleisch, Jennifer, Oliva, Baldomero, Martinez, Javier P., Li, Manqing, David, Michael, Yamagishi, Makoto, Ruiz-Riol, Marta, Brander, Christian, and Tsunetsugu-Yokota, Yasuko
- Subjects
HIV ,T cells ,CD4 antigen ,VIRAL load ,VIRUS reactivation ,GENETIC code - 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. In cell lines and HIV-1 patient PBMCs, the Schlafen 12 protein (SLFN12) is shown to be an HIV-1 restriction factor that inhibits HIV-1 replication and virus reactivation [ABSTRACT FROM AUTHOR]
- Published
- 2023
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