Problems of Virology

Introduction. The persistence of immune dysfunction during therapy has serious consequences for the health of HIV-infected people. Therefore, an important direction is the search for drugs that can reduce the inflammatory potential of the immune system and serve as an additional component of antiviral therapy.

Aim ‒ to study the effect of the immunomodulatory drug Sodium deoxyribonucleate with iron complex (DNA-Na-Fe) on the expression of activation markers in MT-4 cells infected with HIV-1.

Materials and methods. Expression levels of CD4, CD28, CD38, CD62L and HLA-DR proteins on the plasma membrane were measured in cells. To assess viral activity, the p24 protein was quantified by ELISA.

Results and discussion. The two cell variants with different replicative activity were analyzed. Control cells, cells with DNA-Na-Fe, infected cells and infected cells with DNA-Na-Fe were tested. Based on the results obtained, it can be concluded that antiviral activity of the drug in MT-4 cells infected with HIV-1 is associated with immunomodulatory activity that enhances the expression of membrane proteins CD4, CD28, CD38 and CD62L. Diversity in the effect of DNA-Na-Fe on the studied surface proteins expression in two cell lines indicates that they depend on the characteristics of the combined molecular biological processes occurring in cells. And the increased effects observed in a system with changes in replicative activity assumes its active participation in virus replication at the stages of virus penetration and budding.

Conclusion. Studies have shown that DNA-Na-Fe has antiviral and immunomodulatory activity.

Introduction. For four years, SARS-CoV-2, the etiological agent of COVID-19, has been circulating among humans. By the end of the second year, an absence of immunologically naive individuals was observed, attributable to extensive immunization efforts and natural viral exposure. This study focuses on delineating the molecular and biological patterns that facilitate the persistence of SARS-CoV-2, thereby informing predictions on the epidemiological trajectory of COVID-19 toward refining pandemic countermeasures.

The aim of this study was to describe the molecular biological patterns identified that contribute to the persistence of the virus in the human population.

Materials and methods. For over three years since the beginning of the COVID-19 pandemic, molecular genetic monitoring of SARS-CoV-2 has been conducted, which included the collection of nasopharyngeal swabs from infected individuals, assessment of viral load, and subsequent whole-genome sequencing.

Results. We discerned dominant genetic lineages correlated with rising disease incidence. We scrutinized amino acid substitutions across SARS-CoV-2 proteins and quantified viral loads in swab samples from patients with emerging COVID-19 variants. Our findings suggest a model of viral persistence characterized by 1) periodic serotype shifts causing substantial diminutions in serum virus-neutralizing activity (> 10-fold), 2) serotype-specific accrual of point mutations in the receptor-binding domain (RBD) to modestly circumvent neutralizing antibodies and enhance receptor affinity, and 3) a gradually increasing amount of virus being shed in mucosal surfaces within a single serotype.

Conclusion. This model aptly accounts for the dynamics of COVID-19 incidence in Moscow. For a comprehensive understanding of these dynamics, acquiring population-level data on immune tension and antibody neutralization relative to genetic lineage compositions is essential.

Introduction. The World Health Organization considers the values of antibody titers in the hemagglutination inhibition assay as one of the most important criteria for assessing successful vaccination. Mathematical modeling of cross-immunity allows for identification on a real-time basis of new antigenic variants, which is of paramount importance for human health.

Materials and methods. This study uses statistical methods and machine learning techniques from simple to complex: logistic regression model, random forest method, and gradient boosting. The calculations used the AAindex matrices in parallel to the Hamming distance. The calculations were carried out with different types and values of antigenic escape thresholds, on four data sets. The results were compared using common binary classification metrics.

Results. Significant differentiation is shown depending on the data sets used. The best results were demonstrated by all three models for the forecast autumn season of 2022, which were preliminary trained on the February season of the same year (Auroc 0.934; 0.958; 0.956, respectively). The lowest results were obtained for the entire forecast year 2023, they were set up on data from two seasons of 2022 (Aucroc 0.614; 0.658; 0.775). The dependence of the results on the types of thresholds used and their values turned out to be insignificant. The additional use of AAindex matrices did not significantly improve the results of the models without introducing significant deterioration.

Conclusion. More complex models show better results. When developing cross-immunity models, testing on a variety of data sets is important to make strong claims about their prognostic robustness.

Relevance. Influenza A virus is characterized by a segmented single-stranded RNA genome. Such organization of the virus genome determines the possibility of reassortment, which can lead to the emergence of new virus variants. The main natural reservoir of most influenza A virus subtypes are wild waterfowl. Seasonal migrations gather waterfowl from all major migration routes to nesting areas near the northern and southern polar circles. This makes intercontinental spread of influenza A viruses possible.

Objective ‒ to conduct molecular genetic monitoring and study the phylogenetic relationships of influenza A virus variants circulating in Antarctica in 2023.

Materials and methods. We studied 84 samples of biological material obtained from birds and marine mammals in April‒May 2023 in coastal areas of Antarctica. For 3 samples, sequencing was performed on the Miseq, Illumina platform and phylogenetic analysis of the obtained nucleotide sequences of the influenza A virus genomes was performed.

Results. The circulation of avian influenza virus in the Antarctic region was confirmed. Heterogeneity of the pool of circulating variants of the influenza A virus (H3N8, H1N1) was revealed. Full-length genomes of the avian influenza virus were sequenced and posted in the GISAID database (EPI_ISL_19032103, 19174530, 19174467).

Conclusion. The study of the genetic diversity of influenza A viruses circulating in the polar regions of the Earth and the identification of the conditions for the emergence of new genetic variants is a relevant task for the development of measures to prevent biological threats.