Russian Journal of Infection and Immunity
ISSN (print): 2220-7619, ISSN (online): 2313-7398 Founders: Russian Association of Allergologists and Clinical Immunologists Saint-Petersburg Regional Branch, Saint-Petersburg Pasteur Institute, North-Western Department of Medical Sciences Editor-in-Chief: Areg A. Totolyan, academician of RAS, Doctor of Sc., Professor Frequency / Access: 6 issues per year / Open Included in: White List (3rd level), Higher Attestation Commission List, RISC, Scopus, Web of Science Core Collection
Authors who publish with this journal agree to the following terms: Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
Ethical balance of clinical trials in different socio-economic conditions of their implementation
The modern concept of international clinical trials (CT) has reached strict regulation in terms of norms and ethics and is convincingly reflected in a series of current legislative acts, at the global, regional and national levels. Of particular interest in this area are situations of dual loyalty related to moral, financial and legal gradation of research in countries with different levels in economic development and priorities for owning the investigational drug’s patent. Based on this, the new picture of the modern Russia geopolitical map on participation in international research requires adapting and revisiting the series of semantic characteristics. First of all, this concerns a fundamental change in Russia’s status that developed from a region for conducting research on foreign drugs to be further registered, to the position as the sponsor of research on domestic drugs in third countries, usually with limited economic and infrastructural resources. This metamorphosis is not only significant in terms of the qualitative redistribution of roles, but, in connection with the high rates of popularization and real increase in the volume of such research, for example, in Africa, it dictates a need to rethink the entire system of administrative and ethical approaches to their implementation. In this article, a targeted attention is first paid to the factor of special responsibility for the adoption and regulatory consolidation in the Russia the special ethical code for sponsor’s research in the context of their implementation in regions with limited resources. This task is coupled to introducing domestic experience as well as deep legal and information baggage accumulated by international practice into the protocol for the development of sponsor research in the Russia. The specificity is also of special importance because this work consists of the direct authorial involvement in the process for establishing and forming partnership ethical code based on the principles of justice, respect, care and honesty in research with unequal resources.
Copyright (c) 2025 Kubar O.I. https://creativecommons.org/licenses/by/4.0
Tissue-resident memory CD8+ T cells and their role in the immune response to infection and vaccination
A variety of body tissues contain tissue-resident memory CD8+ T cells — long-lived multifunctional effector cells formed during the immune response to infection, which populate previously infected tissue long term. The localization of these cells is determined due to expression of a set of adhesive molecules that hold the cell in a specific tissue microenvironment, as well as the lack of molecules involved in exiting into the blood and lymphatic vessels. The program for establishing such cell phenotype can apparently be launched at various stages of T cell maturation during the immune response. Resident memory CD8+ T cells protect tissues from viruses and other intracellular parasites, kill transformed cells, and in some cases participate in the pathogenesis of immune-mediated inflammatory diseases. The accumulation of resident memory T cells can be induced by vaccination, and targeting these cells by vaccines, along with triggering a protective humoral response, appears desirable for the prevention of many intracellular infections. At the site of pathogen entry, resident memory CD8+ T cells can provide tissue protection quicker than circulating T cells, which is essential for preventing rapidly evolving viral infections. Localization of memory CD8+ T cells in tissues allows the pool of these cells to be increased without obvious restrictions. Accordingly, it is possible to carry out a large number of different vaccinations to stimulate these cells without losing the vaccines effectiveness. Finally, not all pathogens antigenic epitopes recognized by CD8+ T cells undergo rapid and systematic changes such as the surface B-cell epitopes of the same pathogens. Additional recruitment of resident memory CD8+ T cells in response to a vaccine may ensure greater coverage of pathogen variants and contribute to developing heterosubtypic immunity. The review presents data on resident memory CD8+ T cells in various tissues, their participation in the immune response to infections and vaccinations, as well as molecules that control their localization.
Copyright (c) 2025 Talayev V.Y., Babaykina O.N., Svetlova M.V., Zaichenko I.Y., Kurkova E.V. https://creativecommons.org/licenses/by/4.0
Early phases of tuberculosis infection: immune response and host genetic control
Tuberculosis (TB), primarily pulmonary TB, continues to pose a serious threat to public health, despite intensive studies investigating related pathogenesis, as well as development and testing of novel anti-TB drugs and vaccines. One of the reasons for such a slow progress in establishing effective TB spreading control as well as improving TB prophylaxis and treatment is recognized to be due to substantial shortage of our understanding mechanisms on immune response to and genetic control of the infection, as well as key defects interfering with ability of the host to combat progressive disease. Primarily, it is accounted for by the gaps in our knowledge on early phases of infection, because clinicians virtually never experience them in real-world practice, whilst the majority of existing animal models fail to adequately mimic the events occurring in human TB-infected lung. In this review, we briefly outline some unresolved issues related to TB immunity and genetics, specifically focusing at the first month of infection. Herein, we describe interactions between mycobacteria and diverse phagocyte types in the lung tissue as well as the consequences of mycobacterial phagocytosis by alveolar and interstitial macrophages, neutrophils, eosinophils and dendritic cells. Next, the issues concerning tuberculous granuloma classification and relevant functional diversity as well as difference in immunologist and pathologist viewpoint on nature of primary tuberculous lesion are discussed. Finally, the sequence of innate and adaptive immune reactions against mycobacteria, as well as T-cell — neutrophil interplay during TB course gains special attention. Based on personal studies assessing immune response dynamics and expression of immune activation/exhaustion markers on CD4+ T-cells in MHC II allele-specific TB-infected mice we discuss key phenotypes between genetically susceptible and relatively resistant animals.
Copyright (c) 2025 Kondratieva T.K., Kondratieva E.V., Apt A.S. https://creativecommons.org/licenses/by/4.0
Impact of viruses and retrotransposons on genetic instability and aging
Preventive medicine holds significant promise for delaying and even preventing dangerous age-related pathologies. Advances in vaccine development, new preventive medications, cardiovascular implants and early diagnostic tools has increased life expectancy both in Russia and worldwide. Age-dependent genetic instability results in increased risk of developing a number of age-associated diseases. One consequence of this instability is the accumulation of senescent cells across tissues. Senescent cells lose functional activity, replacing normal cells, and are characterized by the secretion of proinflammatory cytokines, creating a chronic inflammatory background, which is the main characteristic of aging. Genetic instability is associated with higher activity of endogenous retroviruses, retrotransposons. Additionally, exogenic viruses and bacteria are able to damage cell genetic apparatus and induce disrupted transcription, translation and repair. The review discusses new approaches aimed at reducing the risk of age-related diseases by controlling genetic instability and viral infections, as well as mechanisms regulating genetic stability. Among the repercussions of disrupting such mechanisms are the development of proliferative, neurodegenerative diseases, cellular senescence and their contribution to chronic inflammation. Antiviral medications and compounds that suppress the activity of endogenous reverse transcriptases are proposed as promising preventive agents for suppressing age-related genetic instability. Although such substances are already used in the clinic to control human immunodeficiency virus, there are currently no medications suitable for long-term use without significant side effects. In this regard, it is primarily important to develop new generation medications that could be used as preventive agents and would meet efficacy and safety requirements, with minimal side effects. The review also explores other promising approaches such as senolytics (agents that selectively eliminate senescent cells) and senomorphics (substances that suppress proinflammatory in prevention of age-associated pathologies. Another perspective method for preventing genetic instability and accumulation of senescent cells is a search for highly specific targets and the development of immunization approaches that allow immune system to remove damaged and senescent cells with increased genetic instability. The proposed approaches can prolong health span and reduce the burden on healthcare system.
Copyright (c) 2025 Lysakova E.V., Burak M.Y., Navrotsky M.B., Rybtsov S.A. https://creativecommons.org/licenses/by/4.0
Interactions Between Viral and Bacterial Pathogens in Infection Development: A Review with an Emphasis on Herpes Simplex Virus (HSV)
The interaction between viruses and bacteria has a significant impact on human health, affecting various microbial ecosystems in the respiratory and urogenital tracts as well as in cases of ventilator-associated pneumonia. These interactions can be complex and contribute to the development of diseases. Some interactions benefit the virus directly, while others indirectly create conditions favorable for bacterial growth. For instance, viruses can damage epithelial cells, disrupt the immune system, and alter the composition of the microbiota, making the host more susceptible to bacterial infections. Conversely, bacterial species can influence viral infections by altering the host environment and potentially contributing to viral transmission. Herpes simplex virus (HSV) is a common infection caused by two types, HSV-1 and HSV-2, which can lead to various illnesses ranging from mild mucocutaneous infections to severe neurological and systemic complications. HSV-1 is often associated with cold sores, while HSV-2 primarily causes genital herpes. Both viruses are highly contagious and spread through close contact. While there’s no cure, antiviral medications can manage symptoms and reduce transmission. The prevalence of HSV-2 varies globally and is influenced by factors such as geographic location, gender, and sexual behavior. The virus can cause a wide range of symptoms depending on the infection site and the individual’s immune system. HSV can interact with various bacterial species to influence the development and progression of disease. For example, it can exacerbate periodontal disease by creating conditions favorable for bacterial growth or increase the risk of acquiring bacterial infections such as Staphylococcus aureus and Acinetobacter baumannii. Conversely, some bacteria, like Lactobacillus crispatus, can inhibit HSV infection. Additionally, HSV can interact with bacteria in specific disease contexts, such as increasing the severity of ventilator-associated pneumonia or facilitating bacterial urinary tract infections. Moreover, bacterial vaginosis is associated with an increased risk of HSV-2 acquisition. Overall, this review underscores the necessity for ongoing research into viral-bacterial interactions, particularly focusing on HSV, to enhance our understanding of disease pathogenesis and improve therapeutic and public health strategies.
Copyright (c) 2025 Kalantar Neyestanaki M., Mehdipour A. https://creativecommons.org/licenses/by/4.0
First data on the molecular genetic diversity of HHV6B and its impact on the clinical and laboratory course of mononucleosis-like syndrome in children
Human herpes virus 6B (HHV6B) is a ubiquitous causative agent of mononucleosis-like syndrome (MLS) and other diseases. The diversity of HHV6B infection may be due to virus genetic polymorphism. Molecular genetic diversity of circulating HHV6B, as well as its impact on the clinical and laboratory features of HHV6B infection have not been studied. The aim of the work was to study the intraspecific diversity of HHV6B circulating among children in Nizhny Novgorod (Russia) region, and to investigate its effect on MLS clinical and laboratory features. Blood leukocytes and saliva DNA samples from healthy children and children with HHV6B infection were analyzed for HHV6B DNA detection. Original intraspecific HHV6B classification based on detecting signature nucleotide substitutions in the sequence of the U90 gene fragment, was used for virus typing. A relationship between HHV6B genovariant and clinical/laboratory MLS characteristics was studied using multivariate statistical methods. Circulation of four HHV6B genovariants was shown among children in Nizhny Novgorod region: HHV6B/GV2e, HHV6B/GV2b (dominant genovariants), HHV6B/GV1a and HHV6B/GV2a (minor genovariants). Children with MLS infected with HHV6B/GV2e genovariant were more likely to have laboratory signs of cytolysis and increased peripheral blood lymphocyte count. Children with MLS infected with the HHV6B/GV2b genovariant were more likely to have higher mature neutrophil level. An increase of HHV6B viral load in leukocytes was accompanied by aggravated intoxication symptoms. Co-infection with the Epstein–Barr virus (EBV) led to more severe symptoms of acute tonsillitis, hepatosplenomegaly, and lymphadenopathy. Patients with EBV were more likely to have higher ALAT and lymphocyte level along with decreased mature neutrophil count. In children with MLS, EBV coinfection caused smaller HHV6B viral load in blood leukocytes (in children with HHV6B DNA 10 or more copies/105 cells) and lower HHV6B DNA detection frequency in saliva (in children with HHV6B DNA less than 10 copies/105 leukocytes). The results show the influence of genetic HHV6B polymorphism upon the clinical and laboratory features of MLS in children, and also demonstrate that HHV6B/GV2e and EBV cause similar disease symptoms.
Copyright (c) 2025 Filatova E.N., Sakharnov N.A., Suslov N.A., Popkova M.I., Utkin O.V. https://creativecommons.org/licenses/by/4.0
Adaptive NK cells acquire B-lymphocyte CD19 surface marker via trogocytosis during activation of chronic EBV infection
In the last decade, there have been reports of NK with low CD19 coexpression in the blood and bone marrow. There is no data on their association with pathology. We have previously shown that CD19+dim NK has an adaptive phenotype. A possible reason for the appearance of CD19 on NK may occur via trogocytosis of B-lymphocytes during active EBV infection. The aim of study is to identify factors contributing to the appearance of a CD56+CD19+dim NK in the peripheral blood of patients with herpes infection. Materials and methods. Blood, saliva, and other biological fluids from 225 patients (34.6±8.5 years, 71% women) were analyzed. Chronic persistent EBV infection was noted in 29%, CMV — in 2.2%, mixed infection — in 10%. IgM to CMV and IgG with avidity were determined in serum; CMV and EBV DNA in biological fluids. Subpopulations of blood lymphocytes were studied by flow cytometry to quantitate CD19+dim NK cell level. In individuals without IgG to CMV, CD19+dim NK were not determined. A relationship was found between the presence of DNA of each virus and the presence of CD19+dim NK cells. The proportion of CD19+dim NK cells peaked at active replication of both viruses and decreased in the absence of CMV replication. Among individuals with mixed infection, cell subpopulation was identified in the group of younger patients with long-term chronic EBV infection. In this group, no significant changes in the content of total immunoglobulins were detected; no diseases in history that suppress an adequate humoral immunity were observed. Among individuals with mixed infection, but without CD19+dim NK cells, a decrease in total immunoglobulins and the presence of diseases leading to altered production of specific immunoglobulins were more often noted. The appearance of CD19+dim NK cells in the blood is facilitated by CMV infection, the presence of long-term chronic EBV infection with activation at the time of the study, and an intact humoral immunity. CD19+dim NK cells are not detected in individuals without IgG to CMV, in the absence of EBV activation, in the presence of diseases that lead to impaired humoral immunity. The appearance of the CD56+CD19+dim NK cells in the blood is a consequence of the participation of adaptive NK cells in the antiviral response with a high level of neutralizing antibodies and a marker of trogocytosis of B-cells that have bound EBV. The possibility of the presence of CD19+dim NK cells in the blood must be taken into account when phenotyping B-cells.
Copyright (c) 2025 Kalashnikova A.A., Bychkova N.V., Rakityanskaya I.A. https://creativecommons.org/licenses/by/4.0
Biological properties and pathogenetic potential of Weeksellaceae family bacteria
In recent years, the role of former saprophyte bacteria in the etiology of human infectious diseases has become an increasingly pressing issue. Of particular interest are non-fermenting gram-negative bacteria, many of which are members of the rhizobiome in some plants, soil and water microbiome. Increasingly, scientific literature covers cases of infections caused by members of the order Flavobacteriales, namely the genus Chryseobacterium, Elizabethkingia and Empedobacter of the Weeksellaceae family. Microorganisms of the latter are causative agents in several human diseases, including urinary tract and respiratory tract infections. The aim of our study was to investigate the biological properties of bacteria of the genus Chryseobacterium, Elizabethkingia and Empedobacter of the Weeksellaceae family isolated from patients with cystic fibrosis and to assess their pathogenetic potential. To analyze the biological properties and pathogenetic potential, 32 clinical strains of bacteria belonging to the Weeksellaceae family, isolated from biological material samples of the respiratory tract from cystic fibrosis patients, were selected for the study. Differential diagnostic media and plate test systems were used. DNA was isolated using 5X ScreenMix (ZAO Evrogen) and PCR with gel electrophoresis was performed. Bacteria of the Weeksellaceae family are characterized by a wide range of enzymes, especially C. arthrosphaerae and E. meningoseptica. It was found that strains of the Chryseobacterium, Elizabethkingia and Empedobacter genus are carriers of virulence genes, exhibit pathogenicity and participate in chronic respiratory infections in patients with cystic fibrosis. Phenotypic methods for studying enzymatic activity showed that all the examined strains of bacteria of the Weeksellaceae family are characterized by gelatinase activity, and representatives of the genus Chryseobacterium spp. — also by the ability to synthesize plasma coagulase. The potential to produce other enzymes of aggression is less pronounced and was strain specific. Analysis of the genetic profile of virulence factors in the studied bacteria showed that in their genome, genes encoding the enzymes lecithinase, hyaluronidase, elastase and hemolysin were most often found, and in bacteria of the genus Chryseobacterium spp. and Empedobacter spp. — neuroaminidase, which contribute to overcoming tissue barriers, pathogen invasion and spread throughout host tissues. The obtained results and scientific literature data indicate a special clinical role for bacteria of the Weeksellaceae family, which determines the importance of a deep study of the biological properties and virulence factors in members of the genus Chryseobacterium spp., Elizabethkingia spp. and Empedobacter spp.
Copyright (c) 2025 Zubova K.V., Kuznetsova V.A., Kanevsky M.V., Kondratenko O.V., Glinskaya E.V., Nechaeva O.V., Afinogenova A.G. https://creativecommons.org/licenses/by/4.0
Assessment of collective immunity to hepatitis E virus in the Saint Petersburg and Leningrad region
Hepatitis E virus (HEV) represents a significant medical and social problem characterized by high prevalence and serious clinical consequences, particularly among vulnerable population groups including pregnant women and individuals with immunodeficiency conditions. The existing insufficient awareness of the disease’s clinical picture combined with limited testing for hepatitis E markers leads to a substantial proportion of undiagnosed infection cases. In the Russian Federation, sporadic outbreaks of HEV infection are observed; however, the complete epidemiological situation remains poorly understood due to objective difficulties in diagnosis and limited availability of specialized laboratory tests. The aim of our study was to assess the true prevalence of anti-HEV antibodies in the population of St. Petersburg and Leningrad region depending on infectious status and socio-demographic characteristics. Methodology. A population-based screening was conducted involving 6773 volunteers aged from 1 year to over 70 years old. Specific IgG class antibodies against HEV were detected using an enzyme immunoassay method with the test system “Vectogep-E IgG”. Results. The results demonstrated that anti-HEV antibodies were present in 5.1% of examined individuals (343 out of 6773), which corresponds to a prevalence rate of 5064.2 per 100 thousand population. There was a statistically significant correlation between age and seropositivity rates, with the highest frequency of antibody detection noted in the older age group (over 70 years). Among those who denied any history of the disease, the antibody detection rate was 5.0%; while among those uncertain about their past health status, this figure reached 8.1%. Significantly higher frequencies of anti-HEV antibody detection were found among individuals with prior surgical interventions or blood transfusions compared to volunteers without such histories. Patients with previously experienced hepatitis A had anti-HEV antibodies at a rate of 6.1%, suggesting possible co-infection by these viral agents. To achieve effective prevention of HEV infections, it is necessary to develop a strategy consisting of three main stages: promoting non-specific preventive measures and increasing public awareness regarding transmission routes and methods of hepatitis E prevention; studying the feasibility and potential benefits of introducing targeted vaccination programs against HEV; conducting further research into population immunity levels to HEV across different regions of Russia to clarify the epidemiological situation and identify potential foci of infection spread.
Copyright (c) 2025 Popova A.Y., Gorbunova A.Y., Ostankova Y.V., Egorova S.A., Reingardt D.E., Ivanova A.R., Shchemelev A.N., Drozd I.V., Zhimbaeva O.B., Danilova E.M., Milichkina A.M., Ezhlova E.B., Melnikova A.A., Bashketova N.S., Buts L.V., Totolian A.A. https://creativecommons.org/licenses/by/4.0
Peripheral blood B-cells and CXCR3 expression in chronic hepatitis C virus infection
Hepatitis C virus (HCV) infection remains a serious global healthcare challenge, often leading to chronic disease with complications such as liver cirrhosis, hepatocellular carcinoma, and extrahepatic manifestations. According to the World Health Organization (WHO), an estimated about 50 million people lived with chronic HCV infection in 2022, highlighting the ongoing need to understand the immune mechanisms driving disease progression. HCV may evade of immunosurveillance, so that disease progression is linked to specific immune response, whereas reactivation risk after antiviral therapy exists, which together account for a need to gain understanding of underlying immune mechanisms. HCV may infect lymphocytes primarily B-cells serving as a virus reservoir and result in diverse systemic complications. The current study focused on analyzing peripheral blood CXCR3+ B-cells at various differentiation stages in patients with chronic HCV infection to assess a potential link to clinical and laboratory markers of disease progression. Blood samples collected from 58 patients with chronic HCV infection and 27 healthy controls were examined. When analyzing flow cytometry data, we noted a significant B-cell redistribution in HCV infection compared to control samples presented as a shift towards activated mature, resting memory and ‘double negative’ B-cells characterized by increased expression of chemokine receptor CXCR3. Flow cytometry analysis revealed no significant difference in total B-cell (CD19+) but elevated memory B-cells (CD27+CD19+) (p = 0.037). CXCR3 expression peaked on memory B-cells and increased across all B-cell subsets in HCV patients (p < 0.001). Redistribution toward differentiated B-cell subsets — double-negative (CD38–CD27–), resting memory (CD38–CD27+), and activated mature (CD38+CD27+) B-cells was observed, with elevated CXCR3+ percentage in the latter two subsets (p = 0.017 and p = 0.001, respectively). HCV viral load correlated positively with CD38+ B-cells and CXCR3+ naïve/activated mature subset counts but inversely with CD38+ B1/B2/memory cell levels. Genotype 1 and advanced fibrosis (F3/cirrhosis) were associated with reduced B2 cells and increased CXCR3+ B1/B2 subset levels. These findings suggest that chronic HCV infection drives B-cell differentiation and CXCR3-mediated recruitment to the liver, implicating CXCR3 in disease progression.
Copyright (c) 2025 Arsentieva N.A., Elezov D.S., Kudryavtsev I.V., Korobova Z.R., Totolian A.A. https://creativecommons.org/licenses/by/4.0
Molecular characterization of PGA gene types A–D among multi-drug resistant strains of Acinetobacter baumannii
This study aimed to explore the prevalence of Acinetobacter baumannii in clinical settings, its antimicrobial resistance, and biofilm formation ability in ventilator-associated pneumonia (VAP) patients, with a particular focus on the pgaABCD gene locus responsible for biofilm formation. A total of 53 isolates were collected over a 5-month period from patients suffering from pneumonia and lower respiratory tract infections. The isolates were identified, and their drug resistance profiles were evaluated using the VITEK automated system. Biofilm formation ability was assessed using the crystal violet assay. The presence of the pgaABCD gene was confirmed through PCR, and the sequences were analyzed to investigate gene prevalence and mutations. Among the 53 clinical samples, 29 isolates (54.7%) were confirmed as A. baumannii. Biofilm formation was detected in 62.1% of the isolates, with varying levels of biofilm production. All 29 isolates (100%) encoded both the pgaA and pgaD genes, while the pgaB and pgaC genes were present in 93.10% and 89.66% of the isolates, respectively. Multidrug-resistant (MDR) strains were prevalent among the clinical isolates, with high biofilm production ability. Sequencing of the pgaABCD genes revealed mutations contributing to the diversity of biofilm formation. This study emphasizes the strong relationship between the pgaABCD locus and biofilm formation in MDR A. baumannii strains. The high prevalence of biofilm-forming isolates underscores the challenges in treating infections caused by A. baumannii, especially in VAP patients. These findings highlight the need for biofilm-targeted treatment strategies to improve patient outcomes in healthcare settings.
Copyright (c) 2025 Supreeta M., Kannika Parameshwari K., Smiline Girija A., Vijayashree Priyadharsini J. https://creativecommons.org/licenses/by/4.0
Regulation of immune response by permafrost microorganism metabolites via effector T-lymphocytes
Infectious agents have closely interacted with the human immune system, acquiring a set of highly sophisticated mechanisms for modulating immunity. One of the survival strategies for viruses, bacteria, protozoa, helminths and fungi is to target the regulatory T cell network (Treg: CD4+CD25hiCD127–) that controls immunopathogenic responses in many infections. Not only pathogens but also commensals are able to directly induce the conversion of naive T cells into suppressive Foxp3-expressing Tregs, while others activate pre-existing natural Tregs, in both cases suppressing pathogen-specific effector responses. However, Tregs can also contribute to immunity under certain conditions, such as at the initial stages of infection when effector cells must gain access to the site of infection, and subsequently in ensuring the generation of effector memory cells. It is noteworthy that currently little information on whether infections selectively drive pathogen-specific Tregs, and if so, whether such cells are also reactive to autoantigens are available. Further analysis of Treg subset specificity, along with a clearer picture of relative dynamics during the disease, should lead to rational strategies of immune intervention to optimize immunity and eliminate the infectious process. Thus, restoration of Treg function is important in the treatment of infectious, autoimmune and other diseases and can serve as a marker of their successful treatment. The article assesses the effect of exometabolites of derived from permafrost Bacillus bacteria obtained at different temperature conditions of their cultivation on the activity of Treg and effector T lymphocyte differentiation. Significant differences were established: secondary microbial exometabolites affect Treg (CD4+CD25hiCD127–) differentiation and expression of activation markers (CD69, CD25, HLA-DR) on CD4+ and CD8+ T lymphocytes. This effect is regulated by the type of metabolites obtained at different temperatures — “cold” (obtained at 5°C of bacterial incubation), “medium-temperature” (at 22°C) and “heat” (at 37°C) metabolites. In this case, an increase in the Treg level is associated with lower differentiation activity of CD4+ T-lymphocytes exposed to “cold” secondary exometabolites, a decrease in the differentiation activity of CD8+ T-lymphocytes treated with “warm” secondary exometabolites, and a roughly equivalent effect on the differentiation activity of CD4+ and CD8+ T-lymphocytes acted upon by “medium-temperature” secondary exometabolites.
Copyright (c) 2025 Petrov S.A., Sukhovey Y.G., Kalenova L.F., Kostolomova E.G., Kastornov A.A. https://creativecommons.org/licenses/by/4.0
Development of a real-time RT-PCR assay for detection of Hendra and Nipah viruses
The article is devoted to the development of a method for detection of viral RNA of two highly pathogenic zoonotic viruses from the genus Henipavirus — Hendra and Nipah using real-time reverse transcription polymerase chain reaction. In the natural environment, these viruses are carried by flying foxes in the family Pteropodidae. Horses and pigs, respectively, are susceptible to infection. The diseases are also transmitted to humans through contact with sick animals, their biological excreta and from person to person. In infected humans and animals, clinical signs of infection may be asymptomatic, or may present with flu-like symptoms at the onset of the disease and progress to neurologic disease and acute respiratory infection, followed by death. In Australia, the subunit vaccine HeV-sG is used against Hendra virus in horses. There is no treatment or vaccine for Hendra or Nipah viruses for humans. The need to develop new detection methods and search for new viral targets remains an urgent task due to the large area of distribution of the described viruses, high contagiousness and mortality of animals and humans. The study describes the original designed primers and probes for conserved regions of the genomes of two viruses: the gene encoding the nucleocapsid protein of Hendra virus and the gene encoding the glycoprotein of Nipah virus. Synthetic controls for the extraction and reverse transcription PCR stages have been created, confirming the quality of the developed method. Biological samples from healthy people (blood plasma, swabs from oral and nasopharyngeal mucous membranes, cerebrospinal fluid) with the addition of artificial controls passed the stages of sample extraction and real-time reverse transcription PCR, thus confirming the quality of control samples. The detection limit of the described viral RNA identification methods was determined as 100 copies/mL for Hendra virus and 1000 copies/mL for Nipah virus. The amplification transit time is less than 90 minutes. The developed method will help in epidemiologic control of the spread of these infections, can be used in the diagnosis of Hendra and Nipah viruses and for solving research tasks to study the properties of these pathogens.
Copyright (c) 2025 Shirobokova S.A., Shabalina A.V., Sukhikh I.S., Chayeb V.A., Dolgova A.S., Dedkov V.G. https://creativecommons.org/licenses/by/4.0
The incidence of BK virus infection in patients with dysfunction of kidney transplant
BK virus-induced nephropathy is an important cause of renal dysfunction, leading to the loss of transplanted kidneys in up to 50% of cases. This study aimed to appraise the incidence of BKV infection among patients who have received kidney transplantation in Iran. In this retrospective cross-sectional study, recipients of kidney transplants in Mashhad Montaserieh Hospital with a rise of 25% or higher in serum creatinine after at least one month of transplantation were evaluated. Those with evidence of BKV infection, including positive serum or urine polymerase chain reaction (PCR) were included. Overall, of 471 patients, 135 cases (28.7%) were diagnosed with kidney transplant dysfunction. BKV infection was diagnosed based on positive PCR in 30 patients (22.2%) and BKV nephropathy was present in 11 patients (8.1%). The most common cause of ESRD (End Stage Renal Disease) was hypertension (33.3%) and the most common dialysis method was hemodialysis (90%). 10 patients had hematuria or pyuria. In 11 patients with pathological results, the most common finding was interstitial inflammation with tubular cytopathic changes (4 patients, 36.4%). Blood levels of cyclosporine were significantly correlated with the time from transplantation to diagnosis, and tacrolimus level was significantly correlated with creatinine level at diagnosis (p < 0.05). Positive urinalysis was significantly associated with the time from transplantation to the diagnosis of kidney dysfunction in the regression analysis (95%CI: –0.30 to –23.45,p = 0.045). The most important predictor of the occurrence of this disorder in kidney transplant patients was the presence of hematuria and pyuria in urine tests. Moreover, the frequency of BK infection was significantly higher in men than in women, while no significant difference was observed between men and women in the control group.
Copyright (c) 2025 Samadi K., Azhdary Moghaddam Y., Zeraati A., Khatibi S., Zeraati T., Ravanshad Y., Jalambadani Z. https://creativecommons.org/licenses/by/4.0
Flow cytometry for assessing blood extracellular DNA fragments level in with post-COVID syndrome convalescent subjects
Patients with COVID-19 are characterized by markedly elevated levels of cell-free DNA in the peripheral blood, and recently neutrophil extracellular trap DNA strands were detected in the blood plasma of individuals with post-COVID syndrome. Purpose of the study — to develop a methodological approach (technology) for detecting cell-free DNA and to assess its level in the blood of individuals with post-COVID syndrome. Materials and methods. The study enrolled patients with post-COVID syndrome who had severe COVID-19 (experimental group, n = 8, aged 53 to 64 years); patients with severe COVID-19 (comparison group I, n = 5, aged 48 to 67 years); apparently healthy volunteers of different age groups: 18–30 years old (comparison group II, n = 12) and over 60 years old (comparison group III, n = 10, over 60 years old), in whose blood there were no specific IgG antibodies to the SARS-CoV-2 virus. The study was performed in microvolume whole blood samples. Results. To determine the content of intracellular DNA fragments in the blood, a flow cytofluorimetric analysis method was developed based on adding a propidium iodide dye solution to the blood together with the CD45-FITC marker used in leukocyte immunophenotyping according to the Lyse/No-Wash protocol to differentiate intact cells from cellular debris. In healthy subjects, after adding a reagent that lyses erythrocytes and fixes leukocytes to the blood, the dye penetrates into the cells and stains only the intracellular DNA in intact diploid leukocytes. The proportion of weak DNA fluorescence signals from extracellular DNA fragments in the total number of pulses recorded by the cytometer in this case not exceeds 3.2 (2.0–5.6)%. With age in case of the disease, this pattern increases to an average of 13.4 (10.1–18.6)%. In individuals with severe COVID-19, very high magnitude of the studied parameter was recorded — at the level of 82 (68.0–88.6)%. In COVID-19 convalescent patients, high levels of extracellular DNA remained for a month, gradually decreasing by the month 3 to 40.5 (27.4–52.0)%. Conclusion. According to the data obtained, the determination of extracellular DNA using the developed technology allows us to characterize the severity of COVID-19 and assess the compensatory capabilities of the body in the post-COVID period.
Copyright (c) 2025 Kravtsov A.L., Klyueva S.N., Kozhevnikov V.A., Bugorkova S.A. https://creativecommons.org/licenses/by/4.0
Non-toxigenic Vibrio cholerae O1 strains that caused gastroenterocolitis in the Zaporizhia and Kherson regions: case reports and pathogen molecular genetic characteristics
In 2023–2024, two cases of gastroenterocolitis caused by non-toxigenic Vibrio cholerae O1 were documented in Zaporizhzhia and Kherson regions. Previously, diseases of this etiology had not been detected in Russia over the last 18 years, although CTX– strains were isolated from water bodies. The aim of the study was to determine the molecular genetic characteristics of clinical strains of V. cholerae O1 isolated in Russia and comparative bioinformatics analysis of their whole genome sequences (WGSs). Materials and methods. The strains were identified in accordance with MUK 4.2.3745-22, sequencing was performed on the MiSeq Illumina platform, bioinformatics analysis — using BioEdit, Vector NTI, CARD and author’s software. Results. A patient from Zaporizhzhia region fell ill after consumption of market foods, and from the Kherson region — after bathing in the sea. Both were diagnosed with acute gastroenterocolitis, in the second case rotavirus was detected along with vibrio. The isolated cultures with identical PCR genotypes were identified as non-toxigenic V. cholerae O1. Both patogens belonged to Ogawa serotype. The WGSs of both strains lacked prophages CTX, preCTX, islands VPI and VSP-II, genes of heat-stable and cholix toxins, proteins OmpT and OmpU, but shared RTX and msh clusters, genes of hemolysin, metallo- and serine proteases; cytotonic factor Cef, represented in two pathogens by different alleles. Significant differences included the presence in the 2024 pathogen of VSP-I island, T3SS cluster integrated into VPI-3, ompW and β-lactamase varG genes which were absent in the 2023 one. The latter contained an incomplete VPI-2 and significantly altered genes rtxA, as well as genes encoding proteases VesC and VchC. On the dendrogram, the isolates formed 2 distant clusters, which also included environmental waterborne strains isolated in other Russian territories in different years; in each cluster all genes had the same repertoires of genetic determinants and gene alleles. These data evidence an opportunity for their long-term preservation in water reservoirs and the absence of importations from abroad. Conclusion. Two new clonal complexes of CTX– V. cholerae O1 have been identified in the territory of Russian Federation. Non-toxigenic strains usually do not cause large-scale epidemiological complications, and the diseases caused by representatives of each complex could be associated with compromised immunity of patients.
Copyright (c) 2025 Monakhova E.V., Kruglikov V.D., Vodop’yanov A.S., Gaevskaya N.E. https://creativecommons.org/licenses/by/4.0
Expression of FOXO1, FOXO3 and BECN1 genes in peripheral blood leukocytes in chronic course of pulmonary sarcoidosis
Among the FOXO (Forkhead box O) family proteins, which are the most studied and widely represented in various human organs and tissues, transcription factors FOXO1 and FOXO3 are of special importance. Numerous studies evidence about their crucial role in maintaining cell metabolism and homeostasis, as well as in the pathogenesis of various pathological conditions. The involvement of the FOXO-signaling pathway in the pathogenesis of pulmonary sarcoidosis is also confirmed by RNA sequencing data. FOXO activation is related to the regulation of autophagy processes, the disruption of which is noted in pulmonary sarcoidosis, a systemic immunoinflammatory disease of unknown etiology, characterized by the formation of epithelioid cell granulomas in various organs, primarily in the lungs. The study was aimed at investigating expression of FOXO1, FOXO3 and BECLN1 genes in peripheral blood leukocytes from patients with chronic pulmonary sarcoidosis compared with apparently healthy donors (control). It is shown that the expression of transcription factors FOXO1 and FOXO3 genes is significantly higher in peripheral blood leukocytes (PBL) from patients with pulmonary sarcoidosis stage II, with chronic course (stabilization of the condition), in the absence of therapy compared to the control (p < 0.01 and p < 0.001). The PBL BECN1 gene mRNA level from patients with chronic pulmonary sarcoidosis is also higher compared to control group. Correlation analysis revealed a close positive relation between the expression of FOXO1, FOXO3 and BECN1 genes, with Spearman rank correlation coefficients comprising 0.69 (FOXO1/BECN1) and 0.61 (FOXO3/BECN1) (p = 0.0002 and p = 0.0016, respectively). Thus, in stage II pulmonary sarcoidosis patients without therapy, FOXO1/3 activation is likely associated with upregulated BECN1 gene expression encoding the autophagy protein BECLIN1 (ATG6). Numerous molecular genetic markers that contribute to the risk of pulmonary sarcoidosis have been identified. Studying the underlying molecular mechanisms is essential to better understand the disease pathogenesis not only allowing to gain insight into the clinical symptomatology but also to predict the disease outcome. In addition, increased knowledge on pathogenesis contributes to developing more targeted, effective and safe treatment methods for pulmonary sarcoidosis, taking into account individual characteristics of each patient’s health status.
Copyright (c) 2025 Malysheva I.E., Balan O.V., Tikhonovich E.L. https://creativecommons.org/licenses/by/4.0
Hepatitis B surface antigen prevalence in pregnant women before and after national vaccinations
Background. Hepatitis B in pregnant mothers can pose a risk to both the mother and the baby. If left untreated or undiagnosed, hepatitis B can be passed from mother to child during childbirth, leading to chronic hepatitis B infection in the baby. However, with proper prenatal care, including testing and vaccination, the risk of transmission can be significantly reduced. This study investigates the hepatitis B surface antigen (HBsAg) prevalence in pregnant women before and after the start of the national hepatitis B vaccination plan. Materials and methods. This cross-sectional study was conducted on all pregnant mothers in Babol County who gave birth between 2018 and 2020. Then the mothers’ information, including a history of vaccination, place of residence, and HBsAg status, was recorded and checked through the online system and their health records. The obtained data were analyzed using SPSS software version 22 and were displayed as frequency and percentage. Qualitative variables were analyzed with Chi-square tests. Finally, with the logistic regression model, we investigated the effect of variables on hepatitis. In all tests, P-value less than 0.05 is significant. Results. The prevalence of positive HBsAg among 11 282 pregnant women in Babol city was 61 (0.5%). The prevalence rate among vaccinated and unvaccinated mothers was 8 (0.2%) and 53 (0.7%), respectively, and this difference was statistically significant (p = 0.001). The Prevalence of positive HBsAg among city and village residents was 26 people (0.4%) and 35 people (0.7%), respectively, and this difference was not significant (p = 0.07). Also, rural (p = 0.02, OR = 1.82, 95%CI: 1.08–302) and unvaccinated (p < 0.001, OR = 3.79, 95%CI: 1.79–8.01) mothers had a higher chance of contracting hepatitis B. Conclusion. The results indicated that national hepatitis B vaccination in newborns has notably decreased infection rates in future childbearing women. Hepatitis B is a preventable disease through vaccination. The vaccine has demonstrated both safety and high immunogenicity. It is crucial to maintain the immunization of newborns and adhere to the screening guidelines for pregnant mothers as outlined in the national program.
Copyright (c) 2025 Hedayati F., Lotfi S., Ebrahimi P., Javanian M., Bayani F., Darbandi Z., Bayani M. https://creativecommons.org/licenses/by/4.0
A rare сase of рulmonary сryptococcosis in a рatient with Wiskott–Aldrich syndrome infected with FLiRT COVID variant
The new COVID FLiRT vs. previous variant does not pose a greater danger; on the contrary, the new strain has a lower pathogenicity, although it is highly contagious. The article describes a rare case of pulmonary cryptococcosis in a patient with Wiskott-Aldrich syndrome co-infected with the FLiRT strain. Case description. Patient G.P., 31 years old, was in hospital for several hours. He was admitted for emergency indications with complaints of inhale chest pain, dry cough, and body temperature increased to 38°C. It is known from the medical history that the patient had been ill for about two weeks. In the last few days, before hospitalization, he noted a rise in body temperature to 37.3–38.1°C, and his cough worsened. In this regard, he called an ambulance and was taken to the emergency room for diagnosis and treatment. In childhood, he was diagnosed with Wiskott-Aldrich syndrome. In recent years, he presented no complaints from the internal organs. According to the epidemiological history, it was revealed that the patient did not travel to endemic regions 2 weeks before the onset of the disease, nor contact with people suspected of being infected with SARS-CoV-2, or patients whose diagnosis was confirmed by laboratory tests. A general blood test revealed leukocytosis, lymphopenia, an increase in procalcitonin to 4 ng/ml. Computed tomography of the chest organs revealed signs of interstitial pneumonia and small foci (2–7 mm) in the surrounding lung parenchyma. Despite the treatment started, a cough with discharged pinkish sputum suddenly began and death occurred. Autopsy showed alternation of moderately airy alveoli with focal emphysematous alveoli. In the lumen of the alveoli, leukocyte infiltration, edematous fluid, foci of granulomas with cryptococci, lymphohistiocytes, macrophages and single multinucleated giant cells were determined, on the interalveolar septa. Conclusion. Based on the pathological examination and the description of one of the presented cases, it can be assumed that the new COVID FLiRT variant in combination with Cryptococcus neoformans can lead to a severe form of the disease.
Copyright (c) 2025 Alpidovskaya O.V. https://creativecommons.org/licenses/by/4.0