Human T-Cell Leukemia Virus Type 1 (HTLV-1) bZIP Factor Requires Cellular Transcription Factor JunD To Upregulate HTLV-1 Antisense Transcription from the 3' Long Terminal Repeat

International audienc

HBZ-mediated shift of JunD from growth suppressor to tumor promoter in leukemic cells by inhibition of ribosomal protein S25 expression

International audienc

HBZ Stimulates Brain-Derived Neurotrophic Factor/TrkB Autocrine/Paracrine Signaling To Promote Survival of Human T-Cell Leukemia Virus Type 1-Infected T Cells

International audienc

DMPK promoter silencing by CRISPRi as a new therapeutic strategy in myotonic dystrophy type 1

"a. IntroductionMyotonic dystrophy type 1 (DM1) is a life threatening disease and causes severe physical and mental disabilities. Unfortunately, there are currently only symptomatic treatments. Therefore, our team aims at elaborating a new curative approach which consists in the DMPK promoter silencing by the CRISPRi system.b. MethodsThe DMPK promoter inhibition capacity of CRISPRi was tested in immortalized myoblasts from DM1 patients. For this purpose, lentiviral particles were produced using CRISPRi plasmids with their own sgRNAs. Next, these myoblasts were transduced and selected with blasticidin. Then, total DMPK mRNA was titrated by RT-qPCR and nuclear DMPK RNA foci were determinated by FISH.c. ResultsSome sgRNAs lead to near 70% inhibition of DMPK transcription as well as foci average particules in DM1 transduced myoblasts.d. ConclusionsThe CRISPRi system is able to efficiently prevent the DMPK mRNA production and foci formation in myoblast.

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease