2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 52(2018) N 4 p. 510-513; DOI 10.1134/S0026893318040118 Full Text

O.V. Kretova, M.A. Gorbacheva , D.M. Fedoseeva , Y.V. Kravatskya , V.R. Chechetkin , N.A. Tchurikov*

Mutation Frequencies in RNAi Targets in HIV-1 Genomes Obtained from Blood Plasma of Patients Receiving Anti-Retroviral Therapy

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia

Received - 2017-10-03; Accepted - 2017-11-07

Gene therapy for AIDS based on RNA interference (RNAi) is currently looked upon as a promising alternative to conventional antiretroviral chemotherapy. The high variability of HIV-1 is the main challenge in developing new approaches to AIDS therapy. To date, about 18 million HIV-1 infected individuals receive antiretroviral therapy worldwide. As of 2017, about 44% of individuals with AIDS received antiretroviral therapy in Russia. Since the RNAs used for efficient RNAi and the corresponding targets in the viral transcript should be perfectly complementary to each other, it is necessary to continuously monitor the nucleotide sequences of clinical HIV-1 isolates obtained from blood and cells of naïve patients and patients receiving antiretroviral therapy. Comprehensive analysis of the mutation frequencies in the viral genome is only possible with deep sequencing approaches. The present paper reports on an analysis of the mutation frequencies in six 100 bp genome regions in clinical HIV-1 isolates obtained from blood plasma of four Russian AIDS patients who have been receiving antiretroviral therapy for several years. These regions contain efficient RNAi targets. The average frequencies of all possible transversions and transitions within the RNAi targets and in their proximity have been estimated. It has been demonstrated that reverse transcriptase inhibition decreases the frequency of a number of reverse mutations. It has been found that mutations in RNAi targets are rarer (5-75 times lower than the mutation frequency for different nucleotide substitutions) than in the adjacent sequences. Our findings speak in favor of these conservative targets for developing new approaches to gene therapy of AIDS.

gene therapy, HIV-1, mutations, antiretroviral therapy, transversions, transitions, RNA interference, ultra-deep sequencing