Six Highly Conserved Targets of RNAi Revealed in HIV-1-Infected Patients from Russia Are Also Present in Many HIV-1 Strains Worldwide
RNAi has been suggested for use in gene therapy of HIV/AIDS, but the main problem is that HIV-1 is highly variable and could escape attack from the small interfering RNAs (siRNAs) due to even single nucleotide substitutions in the potential targets. To exhaustively check the variability in selected...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253117302202 |
| _version_ | 1819042522151780352 |
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| author | Olga V. Kretova Daria M. Fedoseeva Maria A. Gorbacheva Natalya M. Gashnikova Maria P. Gashnikova Nataliya V. Melnikova Vladimir R. Chechetkin Yuri V. Kravatsky Nickolai A. Tchurikov |
| author_facet | Olga V. Kretova Daria M. Fedoseeva Maria A. Gorbacheva Natalya M. Gashnikova Maria P. Gashnikova Nataliya V. Melnikova Vladimir R. Chechetkin Yuri V. Kravatsky Nickolai A. Tchurikov |
| author_sort | Olga V. Kretova |
| collection | DOAJ |
| description | RNAi has been suggested for use in gene therapy of HIV/AIDS, but the main problem is that HIV-1 is highly variable and could escape attack from the small interfering RNAs (siRNAs) due to even single nucleotide substitutions in the potential targets. To exhaustively check the variability in selected RNA targets of HIV-1, we used ultra-deep sequencing of six regions of HIV-1 from the plasma of two independent cohorts of patients from Russia. Six RNAi targets were found that are invariable in 82%–97% of viruses in both cohorts and are located inside the domains specifying reverse transcriptase (RT), integrase, vpu, gp120, and p17. The analysis of mutation frequencies and their characteristics inside the targets suggests a likely role for APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G, A3G) in G-to-A mutations and a predominant effect of RT biases in the detected variability of the virus. The lowest frequency of mutations was detected in the central part of all six targets. We also discovered that the identical RNAi targets are present in many HIV-1 strains from many countries and from all continents. The data are important for both the understanding of the patterns of HIV-1 mutability and properties of RT and for the development of gene therapy approaches using RNAi for the treatment of HIV/AIDS. Keywords: HIV-1, RNAi targets, gene therapy, ultra-deep sequencing, conserved HIV-1 sequences |
| first_indexed | 2024-12-21T09:42:13Z |
| format | Article |
| id | doaj.art-108faf74656441c38a4a0d298be93785 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-21T09:42:13Z |
| publishDate | 2017-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-108faf74656441c38a4a0d298be937852022-12-21T19:08:26ZengElsevierMolecular Therapy: Nucleic Acids2162-25312017-09-018330344Six Highly Conserved Targets of RNAi Revealed in HIV-1-Infected Patients from Russia Are Also Present in Many HIV-1 Strains WorldwideOlga V. Kretova0Daria M. Fedoseeva1Maria A. Gorbacheva2Natalya M. Gashnikova3Maria P. Gashnikova4Nataliya V. Melnikova5Vladimir R. Chechetkin6Yuri V. Kravatsky7Nickolai A. Tchurikov8Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology, 119334 Moscow, RussiaDepartment of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology, 119334 Moscow, RussiaDepartment of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology, 119334 Moscow, RussiaDepartment of Retroviruses, State Research Center of Virology and Biotechnology Vector, 630559 Koltsovo, RussiaDepartment of Retroviruses, State Research Center of Virology and Biotechnology Vector, 630559 Koltsovo, RussiaLaboratory of Post-Genomic Research, Engelhardt Institute of Molecular Biology, 119334 Moscow, RussiaDepartment of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology, 119334 Moscow, RussiaDepartment of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology, 119334 Moscow, RussiaDepartment of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology, 119334 Moscow, Russia; Corresponding author: Nickolai A. Tchurikov, Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology, 119334 Moscow, Russia.RNAi has been suggested for use in gene therapy of HIV/AIDS, but the main problem is that HIV-1 is highly variable and could escape attack from the small interfering RNAs (siRNAs) due to even single nucleotide substitutions in the potential targets. To exhaustively check the variability in selected RNA targets of HIV-1, we used ultra-deep sequencing of six regions of HIV-1 from the plasma of two independent cohorts of patients from Russia. Six RNAi targets were found that are invariable in 82%–97% of viruses in both cohorts and are located inside the domains specifying reverse transcriptase (RT), integrase, vpu, gp120, and p17. The analysis of mutation frequencies and their characteristics inside the targets suggests a likely role for APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G, A3G) in G-to-A mutations and a predominant effect of RT biases in the detected variability of the virus. The lowest frequency of mutations was detected in the central part of all six targets. We also discovered that the identical RNAi targets are present in many HIV-1 strains from many countries and from all continents. The data are important for both the understanding of the patterns of HIV-1 mutability and properties of RT and for the development of gene therapy approaches using RNAi for the treatment of HIV/AIDS. Keywords: HIV-1, RNAi targets, gene therapy, ultra-deep sequencing, conserved HIV-1 sequenceshttp://www.sciencedirect.com/science/article/pii/S2162253117302202 |
| spellingShingle | Olga V. Kretova Daria M. Fedoseeva Maria A. Gorbacheva Natalya M. Gashnikova Maria P. Gashnikova Nataliya V. Melnikova Vladimir R. Chechetkin Yuri V. Kravatsky Nickolai A. Tchurikov Six Highly Conserved Targets of RNAi Revealed in HIV-1-Infected Patients from Russia Are Also Present in Many HIV-1 Strains Worldwide Molecular Therapy: Nucleic Acids |
| title | Six Highly Conserved Targets of RNAi Revealed in HIV-1-Infected Patients from Russia Are Also Present in Many HIV-1 Strains Worldwide |
| title_full | Six Highly Conserved Targets of RNAi Revealed in HIV-1-Infected Patients from Russia Are Also Present in Many HIV-1 Strains Worldwide |
| title_fullStr | Six Highly Conserved Targets of RNAi Revealed in HIV-1-Infected Patients from Russia Are Also Present in Many HIV-1 Strains Worldwide |
| title_full_unstemmed | Six Highly Conserved Targets of RNAi Revealed in HIV-1-Infected Patients from Russia Are Also Present in Many HIV-1 Strains Worldwide |
| title_short | Six Highly Conserved Targets of RNAi Revealed in HIV-1-Infected Patients from Russia Are Also Present in Many HIV-1 Strains Worldwide |
| title_sort | six highly conserved targets of rnai revealed in hiv 1 infected patients from russia are also present in many hiv 1 strains worldwide |
| url | http://www.sciencedirect.com/science/article/pii/S2162253117302202 |
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