Nuclear RNA surveillance complexes silence HIV-1 transcription
| Autor: | Stéphane Pelletier, Lisa Bluy, Gabriel Sanchez, Xavier Contreras, Emmanuelle Beyne, Marion Helsmoortel, Emilie Rousset, Kader Salifou, Sylvie Rouquier, Rosemary Kiernan |
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| Přispěvatelé: | Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
RNA viruses Transcription Genetic [SDV]Life Sciences [q-bio] HIV Infections Pathology and Laboratory Medicine Exosomes Biochemistry Spectrum Analysis Techniques Immunodeficiency Viruses Transcription (biology) Medicine and Health Sciences Small interfering RNAs lcsh:QH301-705.5 Regulation of gene expression education.field_of_study Exosome Multienzyme Ribonuclease Complex Chromosome Biology Nuclear Proteins Flow Cytometry Chromatin 3. Good health Cell biology Virus Latency Precipitation Techniques Nucleic acids Medical Microbiology Spectrophotometry Viral Pathogens Viruses Epigenetics Cytophotometry Pathogens Cellular Structures and Organelles RNA Helicases Research Article Gene Expression Regulation Viral Transcriptional Activation lcsh:Immunologic diseases. Allergy Immunology Population DNA transcription Immunoblotting Repressor Molecular Probe Techniques Biology Research and Analysis Methods Microbiology 03 medical and health sciences Virology Retroviruses Genetics Gene silencing Humans Immunoprecipitation Vesicles education Non-coding RNA Molecular Biology Techniques Psychological repression Microbial Pathogens Molecular Biology HIV Long Terminal Repeat RNA Nuclear [SDV.GEN]Life Sciences [q-bio]/Genetics Lentivirus Organisms RNA Biology and Life Sciences HIV Cell Biology Co-Immunoprecipitation Gene regulation Repressor Proteins 030104 developmental biology lcsh:Biology (General) Exoribonucleases HIV-1 Parasitology Virus Activation Gene expression Carrier Proteins lcsh:RC581-607 HeLa Cells Transcription Factors |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Public Library of Science, 2018, 14 (3), pp.e1006950. ⟨10.1371/journal.ppat.1006950⟩ PLoS Pathogens, Vol 14, Iss 3, p e1006950 (2018) |
| ISSN: | 1553-7366 1553-7374 |
| Popis: | Expression from the HIV-1 LTR can be repressed in a small population of cells, which contributes to the latent reservoir. The factors mediating this repression have not been clearly elucidated. We have identified a network of nuclear RNA surveillance factors that act as effectors of HIV-1 silencing. RRP6, MTR4, ZCCHC8 and ZFC3H1 physically associate with the HIV-1 TAR region and repress transcriptional output and recruitment of RNAPII to the LTR. Knock-down of these factors in J-Lat cells increased the number of GFP-positive cells, with a concomitant increase in histone marks associated with transcriptional activation. Loss of these factors increased HIV-1 expression from infected PBMCs and led to reactivation of HIV-1 from latently infected PBMCs. These findings identify a network of novel transcriptional repressors that control HIV-1 expression and which could open new avenues for therapeutic intervention. Author summary Following integration into the host genome, HIV-1 expression is silenced in a small population of cells, largely via epigenetic mechanisms that repress LTR-mediated transcription. This repression creates a reservoir of cells that prevent an effective cure. It is unclear how and why integrated HIV-1 becomes transcriptionally silenced. Here, we identify a network of nuclear RNA surveillance factors that repress HIV transcription and whose loss increases virus expression in latently infected J-Lat and PBMCs. These findings advance the understanding of transcriptional repression of HIV-1. |
| Databáze: | OpenAIRE |
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