Mutation Frequencies in HIV-1 Genome in Regions Containing Efficient RNAi Targets As Calculated from Ultra-Deep Sequencing Data

• Published in: Molecular biology (New York) Vol. 52; no. 3; pp. 393 - 397
• Main Authors: Kretova, O. V., Gorbacheva, M. A., Fedoseeva, D. M., Kravatsky, Y. V., Chechetkin, V. R., Tchurikov, N. A.
• Format: Journal Article
• Language: English; Russian
• Published: Moscow Pleiades Publishing 01.05.2018; Springer Nature B.V
• Subjects: Acquired immune deficiency syndrome; Acquired Immunodeficiency Syndrome - genetics; Acquired Immunodeficiency Syndrome - therapy; AIDS; Antiviral agents; Biochemistry; Biomedical and Life Sciences; Gene therapy; Genome, Viral; Genomes; Genomics. Trascriptomics; High-Throughput Nucleotide Sequencing; HIV; HIV-1 - genetics; Human Genetics; Human immunodeficiency virus; Humans; Life Sciences; Mutation; Mutation Rate; RNA Interference; RNA, Small Interfering; RNA-mediated interference; siRNA; HIV-1; RNAi; RT; mutations; deep sequencing; gene therapy; transitions; transversions
• ISSN: 0026-8933; 0026-8984; 1608-3245
• DOI: 10.1134/S002689331803007X

HIV-1 is one of the most variable viruses. The development of gene therapy technology using RNAi for AIDS/HIV-1 treatment is a potential alternative for traditional anti-retroviral therapy. Anti-HIV-1 siRNA should aim to exploit the most conserved viral targets. Using the deep sequencing of potential RNAi targets in 100-nt HIV-1 genome fragments from the clinical HIV-1 subtype A isolates in Russia, we found that the frequencies of all possible transversions and transitions in certain RNAi targets are 3–38 times lower than in adjacent sequences. Therefore, these targets are conserved. We propose the development of these RNAi targets for AIDS/HIV-1 treatment. Deep sequencing also enables the detection of the characteristic mutational bias of RT during the replication of viral RNA.