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 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.

Predominance of CRF63_02A1 and multiple patterns of unique recombinant forms of CRF63_A1 among individuals with newly diagnosed HIV-1 infection in Kemerovo Oblast, Russia.

Kemerovo Oblast (KO) has had the highest rate of HIV spread in Russia since 2011. The aim of this work was to study the genetic variation of HIV-1 in Kemerovo Oblast. Blood was sampled from a total of 91 HIV-positive antiretroviral-therapy-naïve individuals in 2013 (38) and 2015 (53). HIV-1 subtypes, pol gene drug resistance mutations, and viral tropism were analyzed. In 2013-2015, the prevalence of HIV-1 subtype A decreased in KO from 60.5 to 7.5 %. The samples collected in 2015 from the patients with newly diagnosed HIV demonstrate the current dominance of HIV-1 CRF63_02A1 (71.7 %) and HIV-1 URF63_A1 (20.8 %), their parental viruses being CRF63_02A1 and subtype A. The initially predominant genetic variant, HIV-1 subtype A, was replaced in KO. An unusually high incidence of HIV-1 unique recombinant forms is probably the result of HIV-1 CRF63_02A1 introduction in the group of injection drug users with the initial HIV-1 subtype A infection and the practice of risky behavior that promotes reinfection. HIV-1 CRF63_02A1, which recently emerged in Siberia, and its recombinant forms have an ever-increasing impact on the current HIV epidemic in Russia, making urgent the need for in-depth study of this HIV-1 genetic variant.

A rapid expansion of HIV-1 CRF63_02A1 among newly diagnosed HIV-infected individuals in the Tomsk Region, Russia.

The prevalence of HIV infection in different Russian regions is nonuniform. In the Tomsk region (TR), 2020 HIV new infection cases were recorded in 2013, the morbidity having increased 5.9-fold as compared to 2012. In total, 64 blood plasma samples from primary HIV cases have been examined. HIV-specific fragments of the pol gene have been obtained for 61 samples (of protease for 58 and of integrase for 23) and of the env gene V3 region for 40 samples. Phylogenetic analysis of the determined HIV-1 sequences has detected CRF63_02A1 in 55 (90.2%) cases, whereas HIV subtype A1, characteristic of Russia, has been observed in only three (4.9%) patients. Three (4.9%) cases contain CRF63_02A1/A recombinant variants. This article demonstrates that a drastic activation of the epidemic in the Tomsk region is accompanied by a rapid spreading of the recently described HIV-1 CRF63_02A1, which we detected in the Novosibirsk region outbreak of 2008.