Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors
| Autor: | Mariana Santa-Marta, João Gonçalves, Carlos F. Barbas, Thomas Gaj, Pedro Ricardo Lucas Perdigao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
RNA viruses CD4-Positive T-Lymphocytes Activating transcription factor lcsh:Medicine Gene Expression HIV Infections Pathology and Laboratory Medicine Hydroxamic Acids Virus Replication Biochemistry Latent Virus Immunodeficiency Viruses Virus latency Medicine and Health Sciences lcsh:Science Promoter Regions Genetic Genetics education.field_of_study Vorinostat Multidisciplinary Histone deacetylase inhibitor Microbial Genetics Activating Transcription Factors 3. Good health Cell biology Enzymes Viral Persistence and Latency Virus Latency Medical Microbiology Viral Pathogens Viruses Viral Genetics Pathogens Oxidoreductases Luciferase medicine.drug Research Article Gene Expression Regulation Viral medicine.drug_class Population DNA transcription Biology Microbiology Cell Line 03 medical and health sciences Virology Retroviruses DNA-binding proteins medicine Humans Gene Regulation education Transcription factor Microbial Pathogens HIV Long Terminal Repeat lcsh:R Lentivirus Organisms Biology and Life Sciences HIV Proteins medicine.disease Regulatory Proteins Histone Deacetylase Inhibitors 030104 developmental biology Viral Gene Expression HEK293 Cells HIV-1 Enzymology lcsh:Q Histone deacetylase Transcription Factors |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 3, p e0150037 (2016) |
| ISSN: | 1932-6203 |
| Popis: | The presence of replication-competent HIV-1 -which resides mainly in resting CD4+ T cells--is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection. |
| Databáze: | OpenAIRE |
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