Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells
Year: 2023
Type: article
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.
Source: Communications Biology
Authors: Mie Kobayashi-Ishihara, Katarína Frazão Smutná, Florencia E. Alonso, Jordi Argilaguet, Anna Esteve-Codina, Kerstin Geiger, Meritxell Genescà, Judith Grau-Expósito, Clara Duran-Castells, Selina Rogenmoser, René Böttcher, Jennifer Jungfleisch, Baldomero Oliva, Javier P. Martinez, Manqing Li, Michael David, Makoto Yamagishi, Marta Ruiz-Riol, Christian Brander, Yasuko Tsunetsugu-Yokota, Maria J. Buzon, Juana Díez, Andreas Meyerhans
Institutions: Universitat Pompeu Fabra, Keio University, Centre de Recerca en Sanitat Animal, Animal Health Research Center, Barcelona Institute of Science and Technology, Centre for Genomic Regulation, Centro Nacional de Análisis Genómico, Universitat Autònoma de Barcelona, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, IrsiCaixa, Hospital Universitari Germans Trias i Pujol, University of California San Diego, Moores Cancer Center, The University of Tokyo, Centro de Investigación Biomédica en Red, Centro de Investigación Biomédica en Red Enfermedades Infecciosas, Universitat de Vic - Universitat Central de Catalunya, Institució Catalana de Recerca i Estudis Avançats, Tokyo University of Technology
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,690
Funders: European Commission, Ministerio de Ciencia e Innovación, National Institutes of Health, Centers for Disease Control and Prevention, Japan Society for the Promotion of Science, Instituto de Salud Carlos III, Agencia Estatal de Investigación, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: G1175115578, G1650125035, Single-Cell Transcriptomic Analysis Reveals Disease-Specific Immune Dysregulation in HTLV-1-Associated Myelopathy., G1855990336, G1934096936, G2262748287, G2309174360, G2601397997, G2660406951, G2672435700, Role of reservoir composition and T cell immunity in HIV rebound kinetics, G300979063, G3480869486, G3518538256, G3680162585, G3681454997, G3690828678, G4042783231, G425668148, G430777504, G434337789, G4637971521, G5080475149, Translational inhibition by Schlafen proteins during the DNA damage response, G5195188938, G526084217, G5337133386, G5421974903, G5648447646, European AIDS Vaccine Initiative 2020, G6366842693, G6767860039, G6975682370, G7084143925, G7223643517, G7434936867, 癌原性物質と生体成分との相互作用にもとずく諸変化と癌化の機序との関連についての物理化学・生化学的研究, G7551257413, 古代説話における諸寺縁起の研究, G775295145, G8130184278, G8684520763, G8696694383, Mechanism of cooperative clonal evolution of ATL by genomic and epigenomic abnormalities, G9000205290, G99296377
OpenAlex ID: W4376133543