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15 pages, 2799 KiB

Open AccessArticle

Promoter Methylation of HIV Coreceptor-Related Genes CCR5 and CXCR4: Original Research

by Anna Esman, Svetlana Salamaikina, Alina Kirichenko, Michael Vinokurov, Darya Fomina, Kirill Sikamov, Arina Syrkina, Anastasia Pokrovskaya and Vasily Akimkin

Viruses 2025, 17(4), 465; https://doi.org/10.3390/v17040465 - 25 Mar 2025

Viewed by 732

Abstract

The persistence of human immunodeficiency virus (HIV) within viral reservoirs poses significant challenges to eradication efforts. Epigenetic alterations, including DNA methylation, are potential factors influencing the latency and persistence of HIV. This study details the development and application of techniques to assess CpG methylation in the promoter regions of the CCR5 and CXCR4 genes, which are key HIV-1 coreceptors. Using both Sanger sequencing and pyrosequencing methods, we examined 51 biological samples from 17 people living with HIV at three time points: baseline (week 0) and post-antiretroviral therapy (ART) at weeks 24 and 48. Our results revealed that CXCR4 promoter CpG sites were largely unmethylated, while CCR5 promoter CpGs exhibited significant variability in methylation levels. Specifically, CCR5 CpG 1 showed a significant decrease in methylation from week 0 to week 48, while CXCR4 CpG 3 displayed a significant decrease between week 0 and week 24. These differences were statistically significant when compared with non-HIV-infected controls. These findings demonstrate distinct methylation patterns between CCR5 and CXCR4 promoters in people living with HIV over time, suggesting that epigenetic modifications may play a role in regulating the persistence of HIV-1. Our techniques provide a reliable framework for assessing gene promoter methylation and could be applied in further research on the epigenetics of HIV. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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13 pages, 1724 KiB

Open AccessArticle

Toll-Like Receptor Genes and Risk of Latent Tuberculosis Infection in People Infected with HIV-1

by Svetlana Salamaikina, Ekaterina Kulabukhova, Vitaly Korchagin, Olga Khokhlova, Konstantin Mironov and Vasiliy Akimkin

Viruses 2024, 16(9), 1371; https://doi.org/10.3390/v16091371 - 28 Aug 2024

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Abstract

The purpose of this study was to determine the contribution of genetic factors, i.e., the level of expression and polymorphisms of Toll-like receptors (TLR), to the susceptibility of latent tuberculosis infection in a Russian cohort of individuals infected with HIV. The patients (n = 317) with confirmed HIV infection were divided into two groups according to the results of the STANDARD E TB-Feron test: 63 cases with a latent TB infection and 274 controls without LTBI. Total DNA and RNA were isolated from whole-blood samples. SNP genotyping and expression levels of five TLR genes (TLR1, TLR2, TLR4, TLR6, and TLR8) were determined by means of real-time PCR. There were no significant differences in the expression levels of the TLRs between the case and control groups. In addition, we did not observe any significant association between the analyzed SNPs and the susceptibility of Latent tuberculosis infection (LTBI) in patients with HIV. However, patients from an entire cohort with the rs4986790-GG (TLR4) and rs5743708-GG (TLR2) genotypes were characterized by lower CD4 T-cell counts compared to carriers of alternative alleles. Moreover, we found a significant risk of a hazardous drop in the CD4 T-cell count below 350 cells/mm³ associated with the rs4986790-G (TLR4) allele. Latent tuberculosis infection in individuals infected with HIV does not significantly modify the level of TLR gene expression. Full article

(This article belongs to the Special Issue HIV and HTLV Infections and Coinfections)

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13 pages, 1870 KiB

Open AccessArticle

Association of Toll-Like Receptor Gene Polymorphisms with Tuberculosis in HIV-Positive Participants

by Svetlana Salamaikina, Vitaly Korchagin, Ekaterina Kulabukhova, Konstantin Mironov, Vera Zimina, Alexey Kravtchenko and Vasily Akimkin

Epigenomes 2023, 7(3), 15; https://doi.org/10.3390/epigenomes7030015 - 25 Jul 2023

Cited by 4 | Viewed by 2303

Abstract

Genetic factors in the HIV-background may play a significant role in the susceptibility to secondary diseases, like tuberculosis, which is the leading cause in mortality of HIV-positive people. Toll-like receptors (TLRs) are considered to be receptors for adaptive immunity, and polymorphisms in TLR genes can influence the activity of the immune response to infection. We conducted a case–control study of the association of TLR gene polymorphisms with the risk of tuberculosis coinfection in a multi-country sample of HIV-positive participants. Our study revealed certain associations between TLR4 and TLR6 polymorphisms and HIV–tuberculosis coinfection. We also found that the analyzed TLR1 and TLR4 polymorphisms were linked with the decline in CD4+ cell count, which is a predictor of disease progression in HIV-infected individuals. Our findings confirm that TLR gene polymorphisms are factors that may contribute to development of HIV–tuberculosis coinfection. However, the essence of the observed associations remains unclear, since it can also include both environmental factors and epigenetic mechanisms of gene expression regulation. Full article

(This article belongs to the Topic Biosocial Studies)

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11 pages, 786 KiB

Open AccessArticle

TLRs Gene Polymorphisms Associated with Pneumonia before and during COVID-19 Pandemic

by Svetlana Salamaikina, Maria Karnaushkina, Vitaly Korchagin, Maria Litvinova, Konstantin Mironov and Vasily Akimkin

Diagnostics 2023, 13(1), 121; https://doi.org/10.3390/diagnostics13010121 - 30 Dec 2022

Cited by 10 | Viewed by 2494

Abstract

Background: The progression of infectious diseases depends on the characteristics of a patient’s innate immunity, and the efficiency of an immune system depends on the patient’s genetic factors, including SNPs in the TLR genes. In this pilot study, we determined the frequency of alleles in these SNPs in a subset of patients with pneumonia. Methods: This study assessed six SNPs from TLR genes: rs5743551 (TLR1), rs5743708, rs3804100 (TLR2), rs4986790 (TLR4), rs5743810 (TLR6), and rs3764880 (TLR8). Three groups of patients participated in this study: patients with pneumonia in 2019 (76 samples), patients with pneumonia caused by SARS-CoV-2 in 2021 (85 samples), and the control group (99 samples). Results: The allele and genotype frequencies obtained for each group were examined using four genetic models. Significant results were obtained when comparing the samples obtained from individuals with pneumonia before the spread of SARS-CoV-2 and from the controls for rs5743551 (TLR1) and rs3764880 (TLR8). Additionally, the comparison of COVID-19-related pneumonia cases and the control group revealed a significant result for rs3804100-G (TLR2). Conclusions: Determining SNP allele frequencies and searching for their associations with the course of pneumonia are important for personalized patient management. However, our results need to be comprehensively assessed in consideration of other clinical parameters. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Pneumonia)

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9 pages, 1309 KiB

Open AccessArticle

SARS-CoV-2 Variants Monitoring Using Real-Time PCR

by Anna Esman, Anna Cherkashina, Konstantin Mironov, Dmitry Dubodelov, Svetlana Salamaikina, Anna Golubeva, Gasan Gasanov, Kamil Khafizov, Natalya Petrova, Evgeniy Cherkashin and Vasiliy Akimkin

Diagnostics 2022, 12(10), 2388; https://doi.org/10.3390/diagnostics12102388 - 1 Oct 2022

Cited by 6 | Viewed by 2583

Abstract

According to the temporary recommendations of the 2021 World Health Organization (WHO), in addition to whole-genome sequencing, laboratories in various countries can also screen for known mutations utilizing targeted RT-PCR-based mutation detection assays. The aim of this work was to generate a laboratory technique to differentiate the main circulating SARS-CoV-2 variants in 2021–2022, when a sharp increase in morbidity was observed with the appearance of the Omicron variant. Real-time PCR methodology is available for use in the majority of scientific and diagnostic institutions in Russia, which makes it possible to increase the coverage of monitoring of variants in the territories of all 85 regions in order to accumulate information for the Central Services and make epidemiological decisions. With the methodology developed by the Central Research Institute of Epidemiology of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing (FSSCRP Human Wellbeing) (CRIE), more than 6000 biological samples have been typed, and 7% of samples with the Delta variant and 92% of samples with the Omicron variant have been identified as of 25 August 2022. Reagents for 140,000 definitions have been supplied to regional organizations. Full article

(This article belongs to the Special Issue Monitoring and Detection for SARS-CoV-2 and Its Variants)

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12 pages, 2206 KiB

Open AccessArticle

Hairy Roots of Scutellaria spp. (Lamiaceae) as Promising Producers of Antiviral Flavones

by Anna Yurievna Stepanova, Aleksandra Ivanovna Solov’eva, Maria Victorovna Malunova, Svetlana Andreevna Salamaikina, Yury Mikhailovich Panov and Andrey Aleksandrovich Lelishentsev

Molecules 2021, 26(13), 3927; https://doi.org/10.3390/molecules26133927 - 27 Jun 2021

Cited by 24 | Viewed by 3601

Abstract

We measured and studied the growth parameters and the qualitative and quantitative composition of the flavones of hairy roots of the Scutellaria genus: S. lateriflora, S. przewalskii and S. pycnoclada. Hairy roots were obtained using wild-type Agrobacterium rhizogenes A4 by co-cultivation of explants (cotyledons) in a suspension of Agrobacterium. The presence of the rol-genes was confirmed by PCR analysis. The hairy roots of the most studied plant from the Scutellaria genus, S. baicalensis, were obtained earlier and used as a reference sample. HPLC-MS showed the predominance of four main flavones (baicalin, baicalein, wogonin and wogonoside) in the methanol extracts of the studied hairy roots. In addition to the four main flavones, the other substances which are typical to the aerial part of plants were found in all the extracts: apigenin, apigetrin, scutellarin and chrysin-7-O-β-d-glucuronide. According to the total content of flavones, the hairy roots of the studied skullcaps form the following series: S. przewalskii (33 mg/g dry weight) > S. baicalensis (17.04 mg/g dry weight) > S. pycnoclada (12.9 mg/g dry weight) > S. lateriflora (4.57 mg/g dry weight). Therefore, the most promising producer of anti-coronavirus flavones is S. przewalskii. Full article

(This article belongs to the Special Issue Flavonoids and Their Disease Prevention and Treatment Potential 2021)

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