title: A new chimeric protein represses HIV-1 LTR-mediated expression by DNA methylase.
abstract: Once the human immunodeficiency virus (HIV) genome is inserted into the host genome, the virus cannot be removed, which results in latency periods and makes it difficult to eradicate. The majority of strategies to eradicate HIV have been based on preventing virus latency, thereby enabling antiretroviral drugs to act against HIV replication. Another innovative strategy is permanently silencing the integrated virus to prevent the spread of infection. Epigenetic processes are natural mechanisms that can silence viral replication. We describe a new chimeric protein (IN3b) that consists of a HIV-1 integrase domain, which recognises the HIV long terminal repeat (LTR) and the catalytic domain of DNA methyltransferase DNMT3b. Our objective was to silence HIV replication by the specific delivery of the catalytic methyltransferase domain to the LTR promoter to induce its methylation. We found that our IN3b chimeric protein was expressed in the nucleus and decreased LTR-associated HIV genome expression and HIV replication. Therefore, the IN3b chimeric protein may be an effective tool against HIV replication and maybe used in a new line of research to induce or maintain HIV latency.
authors.affiliation: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Martinez-Colom
authors.forename: Sandra
authors.initials: S
authors.lastname: Lasarte
authors.forename: Alejandra
authors.initials: A
authors.lastname: Fernández-Pineda
authors.forename: Miguel
authors.initials: M
authors.lastname: Relloso
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Muñoz-Fernández
mesh_terms: D020134:Catalytic Domain; D002467:Cell Nucleus; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D004353:Drug Evaluation, Preclinical; D020868:Gene Silencing; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D016679:Genome, Viral; D057809:HEK293 Cells; D019427:HIV Integrase / Q000235:genetics / Q000378:metabolism; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D016662:Virus Integration; D017735:Virus Latency; D014779:Virus Replication; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D019427:HIV Integrase; D011993:Recombinant Fusion Proteins; D000097584:DNA Methyltransferase 3B