Vol 14, No 2 (2024)

Many RNA viruses have been reported to be oncogenic (or carcinogenic) in a variety of animal and human cancers. The increase in the incidence and prevalence of cancer-causing viruses in human populations can be known as a key precursor to the development of various cancers. The retrovirus family and Hepatitis C virus (HCV) are also reported to cause cancer. Viral oncoproteins such as Tax of HTLV 1 interacts with cellular ubiquitination complex such as cyclindromatosis tumor suppressor, ubiquitin-specific proteases 7, 11, 15 and 20, A-20 and signal-transducing adaptor molecule binding protein-like-1 in order to improve the cellular signaling pathways. The viral oncoproteins binding to DUB, leading to proliferation of virus-infected cells and cell transformation. Proto-oncogenes (c-onc genes) are the cellular form of v-onc genes. The activation of c-onc genes leads to cell growth. C-onc genes are transformed into an oncogenic form by viral infection. C-onc genes play some roles such as protein kinases, growth factors, growth factor receptors, and DNA binding proteins. The study of transforming retroviruses and their oncogenes and the multiple mechanisms deployed by other RNA viruses to use the growth-suppressive and proapoptotic function of tumor suppressor genes has been added to our current understanding of cancer biology. Oncogenic RNA viruses are important experimental models to study molecular investigation such as cellular networks, including the discovery of oncogenes and tumor suppressors. Understanding of different strategies of RNA viruses as well as the function of their proteins helps to make more extensive plans regarding the adoption of follow-up, prevention and treatment strategies in cancer patients caused by viral origin.

Introduction. Viral capsid proteins can assemble into virus-like particles lacking infectivity and bearing parental virus antigens or artificially introduced antigens from other pathogens. At least some of such particles are highly immunogenic and could serve as a platform for promising vaccines. In this work, we assessed an effect of virus-like particles decorated with a SARS-CoV-2 spike protein fragment on human dendritic cell phenotype and functional properties. Materials and methods. The virus-like particles were assembled using chimeric molecules obtained by fusing genetic sequences encoding a norovirus major capsid protein VP1 fragment and a coronavirus spike protein fragment, including the receptor-binding domain. Dendritic cells were obtained from monocytes in vitro. Results. Incubation of immature dendritic cells with virus-like particles induced their phenotypic and functional maturation. The former was revealed by significantly increased expression of HLA-DR, CD80, CD86 and CD83. Dendritic cell phenotype after incubation with virus-like particles at the maximum concentration of 10 μg/ml did not differ significantly from that of mature dendritic cells in positive control. Along with phenotypic maturation, virus-like particles caused a manifold increase in the production of pro-inflammatory tumor necrosis factor-α, anti-inflammatory interleukin-10, as well as interleukin-6, which can stimulate both antibody synthesis and cellular pro-inflammatory reactions. The pronounced stimulation of dendritic cells by virus-like particles coated with coronavirus antigens evidence about successful particle recognition. Finally, we discuss plausible mechanisms for recognition of such virus-like particles by dendritic cell receptors. Conclusion. It has been shown that chimeric virus-like particles induced phenotypic and functional dendritic cell maturation, which is manifested by markedly elevated expression of functionally important membrane molecules, as well as a manifold rise in production of cytokines with a wide functional range. In our opinion, the data obtained indicate a promise of using virus-like particles based on norovirus proteins to display SARS-CoV-2 antigens.

Sarcoidosis and tuberculosis are both granulomatous diseases that have many similarities, making the differential diagnosis of sarcoidosis and tuberculosis difficult, as well as leading to inappropriate treatment selection of both diseases. Autoimmune inflammation (AI) is one of the processes identified tuberculosis and sarcoidosis. Current evidences about the risk and clinical outcomes of COVID-19 infection in patient with sarcoidosis and M. tuberculosis co-infection are still not well understood. SARS-CoV-2 has direct damage to the epithelial cells of the respiratory system, and in-directly due to circulatory disorders. Materials and methods. In the study we analyzed characteristics of autoimmune response in patients with granulomatosis diseases (tuberculosis and sarcoidosis) after COVID-19. We have analyzed articles for the period of December 2019 to March 2023, published in international database (“Medline”, “PubMed”, “Scopus”). The keywords we used “COVID-19”, “SARS-CoV-2”, “tuberculosis”, “sarcoidosis”, “granulomatosis diseases”, “T cells”, “B cells”, “Treg”, “follicular Treg” and “Treg subsets”. The narrative review was carried out in accordance with the PRISMA protocol (http://www.prisma-statement.org) used for this type of study (ID-423604). Results. The influence of COVID-19 infection can also make a significant contribution to the violation of the T- and B-cell immune response, the violation of the nature of cellular metabolism, which will affect the course of granulomatous inflammation in various ways. According to the different researches, autoimmune inflammation can be an important protective mechanism in sarcoidosis and, at the same time, exacerbates the course of tuberculosis infection with the disease progression and pathogen drug resistance formation subsequently. The study of immune response features in patients with COVID-19 showed the presence of several similar characteristics in cellular components of the immune response. Conclusion. Evidence of the presence of autoimmune inflammation in patients with these granulomatous lung diseases, the development of patient immunotypes, including the transferred COVID-19, will be a significant contribution to the development of personalized patient management tactics, taking into account the identified violations of the immune response mechanisms.

Relevance. Studying features of innate and adaptive mechanisms of immune response in medical workers (MW), the most vulnerable social group with a high risk of infection, is an urgent research task. The aim of the study: Comprehensive study of innate and adaptive immune mechanisms and analyzing relationships between clinically significant polymorphisms (SNPs) in TLR2, TLR4 genes, TLR2 expression level on peripheral blood monocytes, peripheral blood cytokine profile (IL-1β, IL-10, IL-6, IFNγ, platelet activation marker) and SARS-CoV-2-specific humoral immune response in medical workers (MW) at a temporary infectious disease hospital in early and late COVID-19 convalescence. Materials and methods. immunologic, cytofluorimetric and molecular-genetic research methods were applied. Adaptive immune response in medical workers — COVID-19 convalescent subjects. Results. Early post-COVID-19 convalescence period in MW was linked to higher TLR2 monocyte expression; the mean fluorescence intensity was significantly elevated by 1.5-fold compared to control group. Late convalescence period (7 months post-COVID-19) was characterized by lowered serum IFNγ level. A decline in IFNγ production was significant: decreased by 82-fold in MR that was markedly stronger compared to control group (59 times). The imbalance of cytokines controlling antiviral innate and adaptive immune response was revealed in MW with identified combination of polymorphisms rs5743708 and rs4986790 in TLR2, TLR4 genes with the rate not exceeding 6.7%. It was found that 7 months after COVID-19 there was a markedly decreased IFNγ, IL-1β and IL-10 levels. The studies indicate both altered innate and adaptive immune mechanisms and a need to optimize therapeutic and prophylactic measures aimed at increasing patient-intrinsic resistance, protection of respiratory tract mucosal barriers and identification of genetic predictors of defects in innate and adaptive immune response in medical workers — COVID-19 convalescent subjects.

Despite the fact that the state of the individual’s immune system plays an important role in developing community-acquired pneumonia, its clinical features are determined not only by immune response characteristics, but also by the nature of the infectious agent. The aim of the work was to assess immune status of patients with community-acquired pneumonia with lung damage ranging from 2 to 12%, in whom pathogens of a viral, bacterial and fungal nature were verified (n = 96, aged 46,3±20,5) who were admitted to the hospital 5–7 days after disease onset. Materials and methods. The selection of smears and sputum specimens was carried out on day 1 after admission. COVID-19 pathogen was analyzed in smears by PCR using the Vector-PCRR-2019-nCoV-RG kit (SSC Vector of Rospotrebnadzor, Russia). Biochemical activity, colony morphology, and pathogen concentration (in the amount of ≥ 10⁵ CFU/ml) were also evaluated. Based on the results of preliminary studies, target patients groups were formed: with a new coronavirus infection caused by the SARS-CoV-2 gene variant B.1.1.529 (Omicron) (n = 33); with COVID-19 and bacterial pathogens (n = 17); with COVID-19 and combined bacterial and fungal infection (n = 16); patients with identified pathogens of bacterial infections (n = 13); patients with combined bacterial and fungal infection (n = 17). The relative and absolute level of CD45⁺CD3⁺ lymphocytes, CD45⁺CD3⁺CD4⁺ cells, CD45⁺CD3⁺CD8⁺ lymphocytes, CD45⁺CD3-CD16⁺CD56⁺ cells, CD45⁺CD3⁺CD16⁺CD56⁺ lymphocytes, CD45⁺CD45RO^–CD45RA⁺ and CD45⁺CD45RO⁺CD45RA^– lymphocytes, CD45⁺CD19⁺ cells, CD45⁺CD5⁺CD19^–CD27^– and CD45⁺CD19⁺CD5^–CD27^– lymphocytes, CD45⁺CD19⁺CD5^–CD27⁺ cells was assessed in all volunteers. Results. The analysis of the immune status of patients with community-acquired pneumonia associated with Omicron gene variant new coronavirus infection revealed T-lymphocytopenia, a decreased number of CD8⁺ lymphocytes, an increased relative and absolute number of NK cells. In COVID-19 patients, who also had bacterial pathogens verified, there was a decrease in relative and absolute number of T-helper cells, an increased relative and absolute number of B and B2 lymphocytes. In COVID-19-negative volunteers with bacterial and bacterial-fungal community-acquired pneumonia, the relative and absolute level of B and B2 lymphocytes, as well as the general memory B cell population, was increased. In contrast to COVID-19-positive patients, in the absence of T-lymphocytopenia, a decreased number of CD4⁺ cells and rise in number of cytotoxic lymphocytes were recorded in patients of these groups. Conclusions. The data obtained indicate that in the immune status of patients with community-acquired pneumonia, depending on the nature of the infectious agent, changes in relative and absolute level of T-helper cells, cytotoxic lymphocytes, as well as in the qualitative and quantitative B-lymphocyte population composition are recorded.

The main goal of this paper is to delve into a crucial epidemiological metric the daily infection fatality rate in the context of the ongoing COVID-19 pandemic. The significance of understanding this metric lies in its potential to provide insights into the severity and impact of the virus on a daily basis. Methods: To achieve this overarching objective, we employ a comprehensive approach by applying various hybrid models that hybridize both machine learning and statistical techniques. In our pursuit of a deeper understanding, we leverage advanced machine learning algorithms, including Support Vector Machine and Random Forest. These techniques allow us to capture intricate patterns and relationships within the data, contributing to a more nuanced analysis of the infection fatality rate. The application of machine-learning models in epidemiological studies has gained prominence due to their ability to adapt to complex and evolving patterns inherent in infectious disease dynamics. Complementing our machine-learning arsenal, we integrate traditional statistical models such as ARIMA (AutoRegressive Integrated Moving Average), fractional ARIMA, and BATS (Bayesian Structural Time Series). Results. To assess the performance of these models, we employ key evaluation metrics, including Root Mean Squared Error (RMSE), Mean Squared Error (MSE), and Mean Absolute Error (MAE). These metrics serve as critical benchmarks, allowing us to quantify the accuracy and reliability of our models in predicting the daily infection fatality rate. A meticulous evaluation of model performance is crucial for ensuring the validity and of our findings. According to these measures, we see that hybrid models performed well especially ARIMA-RF model RMSE: 0.29, MSE: 0.084, MAE: 0.215 for the horizon 60 and for horizon 120 ARIMA-RF still the best performance, RMSE: 0.268, MSE: 0.071, MAE: 0.183, we get these results due to the capacity of this approach to handle complex patterns contrarily to other model ARIMA, BATS, RF and SVM. Conclusion. This work adopted this approach in order to build a model to predict infection fatality rate, we aspire to provide a nuanced understanding of the factors influencing the severity of the virus, ultimately contributing to the ongoing discourse on effective public health interventions and mitigation strategies.

Recent studies indicate that a marked percentage of chronic viral hepatitis B patients is coinfected with hepatitis D virus known to accelerate the progression of liver disease and contribute to unfavourable disease outcome. Data on premature mortality assessed by the Lost Years of Potential Life (LYPL) indicator, provide the most accurate social burden estimate for such coinfection able to contribute to strengthening viral hepatitis control measures. The aim of the study was to conducting comparative LYPL analyses due to acute and chronic hepatitis B infection without and with delta agent in the Kyrgyz Republic in the years 2014–2018. Materials and methods. LYPL magnitude was calculated using the number of recorded deaths in the reporting form of the 2014–2018 National Statistics Committee «C51-Distribution of deaths by sex, age groups and causes of death». Results. In 2014–2018, 145 cases of death of patients with viral hepatitis B without (HB) and with a delta agent (D) were registered in the Kyrgyz Republic. Of these, 66% (96/145) of patients died from hepatitis B, of which a third (32/96) had an acute disease course. And among those who died from hepatitis D (19/49), acute course was registered in 39%. LYPL for the 145 deceased patients totaled 3766 years, of which 63% (2365 years) were due to HB. Despite that only 35% of patients (51/145) died from acute forms of such hepatitides, their LYPL accounted for 52% (1968) of total years lost that decreased by 4.5-fold for 2014–2018 due to AHB (6.3‰ and 1.41‰, 2014 and 2018, respectively) but increased by 1.1-fold due to AHD (2.7‰ and 3.1‰, 2014 and 2018, respectively). Chronic hepatitis B vs CHD resulted in 1.6 times higher LYPL magnitude (1108 and 691, respectively). At the same time, LYPL due to CHB dynamically increased by 2.6 times, whereas due to CHD — by 6.3 times. Сonclusion. The high LYPL level due to hepatitis B and D infection related to pediatric cases evidence about a heavy burden of such diseases in the Kyrgyz Republic. The data obtained prove that it is necessary to increase adherence of adult population to hepatitis B vaccination and examine children at the site of infection, regardless of vaccination history. Abruptly increased LYPL due to chronic hepatitis cases requires strengthening secondary prevention measures and ensuring timely access to specialized care at infection sites. It is also necessary to evaluate epidemiological surveillance after fatal viral hepatitis.

Coinfection with the human immunodeficiency virus (HIV) and Epstein–Barr virus (EBV) represents a current biomedical problem. The purpose of the study was to evaluate blood leukocyte EBV detection rate and viral load in adult HIV-infected patients. Materials and methods. There were examined blood leukocytes collected from 138 HIV(+) and 68 HIV(–) individuals aged 20–69 years. Statistical analysis was carried out differentiated according to the stages of HIV infection, the CD4⁺ T-lymphocyte count, and adherence to antiretroviral therapy. Results. It was shown that EBV DNA was detected significantly more often in HIV(+) vs HIV(–) individuals (70.3±3.9% and 48.5±6.1%, p = 0.008), with EBV viral load comprising 18 [5; 139] versus 2 [1; 3] copies/10⁵ cells (р < 0.001), respectively. It has been shown that the group of HIV(+) patients is heterogeneous in the frequency of EBV detection and viral load, with the peak EBV frequency (86.7±6.2%) and DNA (121 [34; 252] copies/10⁵ cells) level observed in “naive” patients with severe immunodeficiency. Among “experienced” patients receiving therapy, the relative risk of detecting EBV DNA with low treatment adherence was significantly higher compared to those who developed high adherence (р < 0.05). When the HIV viral load reached undetectable level, EBV DNA concentration was significantly lower where HIV RNA was detectable (1 [0; 8] versus 15 [1; 162] copies/10⁵ cells, р < 0.001). Detection of EBV DNA is associated with higher HIV viral load level and lower CD4⁺ T-lymphocyte count compared to patients with undetected EBV DNA. A relationship has been established between the CD4⁺ T-lymphocyte count in HIV(+) patients and the likelihood of active EBV infection. A threshold cut-off of 200 cells/μl was determined. CD4⁺ T-lymphocyte count < 200 cells/μl vs ≥ 200 cells/μl (р < 0.001) is associated with a 3.3-fold higher risk of detecting active EBV infection. Conclusion. It is necessary to continue interdisciplinary research to improve early diagnostics of EBV-associated diseases in HIV-infected individuals.

Introduction. Optimization of the vaccine-induced T-cell repertoire is one of the strategies to expand the spectrum of protective potential for live attenuated influenza vaccine (LAIV). LAIV cross-protective properties can be improved by introducing the nucleoprotein (NP) gene derived from epidemic parental virus into vaccine strain genome, i.e. by replacing the classical 6:2 genome formula with 5:3. The main objective of the present study was to detail evaluation for virus-specific systemic and tissue-resident memory T-cells subsets in mice immunized with seasonal H1N1 LAIV of the genome formula 6:2 and 5:3. Materials and methods. Two H1N1 LAIV strains with varying NP genes (LAIV 6:2 and LAIV 5:3) were generated using reverse genetics techniques. C57BL/6J mice were immunized intranasally with the vaccine candidates, twice, 3 weeks apart. Cells from the spleen and lung tissues were isolated 7 days after booster immunization to be stimulated with whole H1N1 influenza virus for assessing cytokine-producing memory CD44⁺CD62L– T-cells as well as expression of CD69 and CD103 surface markers using flow cytometry. Humoral murine serum immunity against H1N1 virus was assessed by ELISA. Results. The LAIV 5:3 vs classical 6:2 vaccine strain carrying the epidemic parental NP gene induced significantly more pronounced humoral immune response against recent influenza virus. The group of mice immunized with LAIV 5:3 demonstrated higher levels of virus-specific CD4⁺ and CD8⁺ effector memory T cells (T_EM) in the spleen, including a subset of polyfunctional (IFNγ⁺TNFα⁺IL-2⁺) CD4⁺ T_EM, compared to LAIV 6:2 group. Virus-specific memory T cell levels in lung tissues after immunization with LAIV 5:3 vs LAIV 6:2 also tended to increase, but no significant difference in stimulated tissue-resident CD69⁺CD103^– and CD69⁺CD103⁺ T cells between the groups were found. Conclusion. Modification of the seasonal LAIV strain genome for updating its epitope composition allowed to enhance the virus-specific T-cell immune response both at systemic level and in lung tissues, thereby shoeing that the effectiveness of the vaccine against circulating influenza viruses can be potentially increased.

One of the most common arboviruses in the world are representatives of the genus Orthoflavivirus (family Flaviviridae). On the territory of the Republic of Guinea, the circulation of such representatives of this family as the yellow fever virus (YFV), West Nile virus (WNV) and dengue virus (DENV) has been confirmed. The aim of the study was to determine the level of specific IgG class antibodies to YFV, DENV and WNV in residents of various landscape– geographical zones of the Republic of Guinea by the ELISA method. Materials and methods. For the study, a panel of 1559 blood serums from practically healthy people was compiled, which were collected in all landscape and geographical zones of the Republic of Guinea. The detection of specific IgG class antibodies to DENV and WNV was carried out with commercial diagnostic drugs, and for YFV — with an experimental ELISA test system based on an analogue of the third domain of protein E obtained at the State Research Center for Virology and Biotechnology “Vector” of Rospotrebnadzor. Results. When testing blood sera in 28.5% (95% CI: 26.3–30.7) of cases, IgG antibodies to YFV, to DENV — in 11.8%, (95% CI: 10.3–13.5) and to WNV — in 27.0% (95% CI: 24.8–29.3) were detected. Antibodies to three viruses simultaneously (YFV, DENV and WNV) were detected in 30 cases, to YFV and DENV — 14, YFV and WNV — 44, DENV and WNV — 56. Conclusion. The detection of antibodies to WNV and DENV confirms the fact of the continued circulation of these pathogens in the territory of the Republic of Guinea, which poses a health risk to the local population. A detailed study of the molecular genetic and antigenic properties of flaviviruses circulating in this area will allow the development of more specific diagnostic tools.

Stenotrophomonas maltophilia is an emerging aerobic, non-fermentative, gram-negative multidrug-resistant global opportunistic bacillus. S. maltophilia causes a wide range of infections including respiratory tract infections, blood stream infections and, less commonly, biliary tract infections, skin and soft tissue infections, as well as bone and joint infections. It is increasingly being reported to cause urinary tract infections (UTIs). As for the case report, a 87-year-old male patient visited the Biopathology Laboratory of Nikea Primary Healthcare Center, Piraeus, Greece, for routine examination, being referred by the family doctor (GP). Patient history revealed diabetes mellitus type 2, arterial hypertension, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, chronic obstructive pulmonary disease, diagnosed before 30 years prostate cancer Gleasongrade 6, operated before 15 years, followed by hormone therapy and radiation therapy. Patient history also revealed urinary tract stones with 3 episodes of obstructive pyelonephritis during the last 5 years, followed by hospital admissions and administration of intravenous antibiotic treatment. During the hospital admissions, he had a permanent bladder catheter and received special antimicrobial treatment, for various microorganisms detected in his urine samples, such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Enterococcus faecalis. Urinary incontinence has been a symptom for 15 years, after the prostate cancer surgery. Moreover, during the last 5 years, the patient faced many difficulties in his daily life because of the urinary incontinence. The situation was managed by bladder catheterisation, which further worsened his condition with recurrent UTIs and new episodes of pyelonephritis with subsequent hospitalization. Urinalysis showed proteinuria, intense pyuria, abundance of micro-organisms and abundance of red blood cells. The urine culture grew monomicrobial Stenotrophomonas maltophilia > 10⁵ CFU/ml. The bacterium was identified by the RapID™ REMEL ONE identification system (Thermo Fisher Scientific). Antimicrobial susceptibility testing revealed susceptibility to Trimethoprime/Sulfamethoxazole, Levofloxacin, Ceftriaxone and moderate susceptibility to Ciprofloxacin and Norfloxacin.The patient received treatment with Trimethoprime/Sulfamethoxazole.