Anatomical and physiological aspects of the HIV infection pathogenesis in animal models

Understanding the entire pathogenesis of HIV infection, from penetration at the gates of infection to the induction of severe immunodeficiency, is an essential tool for the development of new treatment methods. Less than 40 years of research into the mechanisms of HIV infection that lead to the development of acquired immunodeficiency syndrome have accumulated a huge amount of information, but HIV's own unique variability identifies new whitespaces. Despite the constant improvement of the protocols of antiretroviral therapy and the success of its use, it has not yet been possible to stop the spread of HIV infection. The development of new protocols and the testing of new groups of antiretroviral drugs is possible, first of all, due to the improvement of animal models of the HIV infection pathogenesis. Their relevance, undoubtedly increases, but still depends on specific research tasks, since none of the in vivo models can comprehensively simulate the mechanism of the infection pathology in humans which leads to multi-organ damage. The aim of the review was to provide up-to-date information on known animal models of HIV infection, focusing on the method of their infection and anatomical, physiological and pathological features

Accumulated experience and future prospects of <i>in vivo</i> hepatitis B virus research

Nowadays, an estimated more than 300 million people live with hepatitis B virus (HBV) infection globally. One of the main goals of the World Health Organization (WHO) is to eliminate viral hepatitis by the year 2030. The study of the pathogenic and immunologic properties of HBV, as well as therapeutic substances and treatment regimens, is significantly complicated by the insufficient number of susceptible biological test subjects (animal models) and the lack of zoonotic reservoirs of the virus. In this regard, researching the properties of HBV and related hepadnaviruses provides invaluable material for understanding the biology of the pathogen and the developing methods of prevention and control of this chronic infectious disease, leading to severe hepatopathies (cirrhosis and hepatocellular carcinoma). Furthermore, prolonged HBV viremia leads to depletion of the immune system, reducing resistance against pathogens of other infections, especially those with a chronic course and socially determined spread. The aim of this research is to evaluate existing animal models of HBV infection in the context of pathogenesis, immunologic and pathomorphological features. For the first time, the hypothesis of the possible use of certain models for the research of HBV-associated socially significant infections is considered from the point of view of the development of pathomorphological features. To complete this review, we analyzed the information about the features of HBV infection models in vivo, published over the last 25 years in open sources (Web of Science, PubMed, Scopus, ScienceDirect, Springer). The main criteria for literature selection were the type of infecting agent, the observed immunologic features of the course of the infectious process and the availability of a description of the pathomorphological features in model organisms

Sequence analysis of the non-coding control region of John Cunningham virus isolates from patients with multiple sclerosis treated with natalizumab

Introduction. The John Cunningham virus (JCPyV) causes a fatal demyelinating disease of the central nervous system known as progressive multifocal leukoencephalopathy (PML). In healthy people, the JCPyV non-coding control region (NCCR) is not rearranged, while NCCRs in immunocompromised patients are characterized by frequent rearrangements and can be associated with PML development. Therefore, patients treated with natalizumab, which decreases the migration of leukocytes and monocytes through the blood-brain barrier to inflammatory foci, are at increased risk of developing PML. The purpose of the study was to analyze NCCR sequences of JCPyV isolates from patients with multiple sclerosis (MS) treated with natalizumab. Materials and methods. A total of 26 blood plasma samples and 8 cerebrospinal fluid samples were analyzed using nested PCR to study the JCPyV NCCR structure in Russian MS patients treated with natalizumab. The NCCRs present in the samples were cloned and sequenced by Sanger sequencing. All the JCPyV NCCR sequences were compared with the archetype sequence and mapped. The NCCR sequences were also examined for presence of putative transcription factor binding sites. Results. A total of 48 NCCR sequences were found. The analysis showed that up to 55% of NCCRs were identified as rearranged NCCRs, while the other were archetype-like NCCRs. All the sequences can be divided into 6 types with one dominant rearrangement pattern. This rearranged NCCR was also found in a patient with the confirmed PML diagnosis and a poor prognosis. All the rearranged NCCRs were characterized by the presence of additional transcription factor binding sites. Conclusion. The study has helped identify previously unknown NCCR patterns typical of MS patients treated with natalizumab in Russia, thus confirming the need for the further research on NCCR rearrangements in MS patients undergoing natalizumab treatment to gain better understanding of the origin of neurovirulent JCPyV variants

“Folk History” of the Battle of Stalingrad (Based on the Materials of the Research Project “Stalingraders in the Battle of Stalingrad”)

In 2012–2013, a project of high social significance, novelty, and a scientific challenge was implemented in Volgograd. The goal of the project was to prepare the manuscript of a biographic encyclopedia “Stalingraders in The Battle of Stalingrad”. The database of sources that have never been published consists of materials of 80 museums and archives of Volgograd and 30 municipal subjects of the Volgograd region. The novelty of the project consists in the fact that it constitutes the first case of biographic and prosopographic research on the local aspect of the battle. The manuscript includes more than 5 000 biographic articles. The project bears high social significance since it generalizes the data on people for whom the Battle of Stalingrad was the battle for their “little Motherland”. Introducing the biographies of Stalingraders into the research has a memorial goal. The research problems under the project are also important. The new research paradigm, defined as “human dimension of war” leads to collecting a huge amount of empirical data. The idea of the project, as well as the difficulties in its completion, are very characteristic for the current stage of Russian research of the Great Patriotic War. Data collection, large-scale search projects on war cites, interest to all new resources go beyond the professional society of historians. However, generalizing this material, and verifying sources remains within the competence of experts. The historians must evaluate the conceptual idea of quantitative methods in studying war history of Russia. In the project, the quantitative methods lead to supported conclusions about close interaction of the front and the rear at the level of everyday life; they remove the stereotypes of exclusively sacrificial role of civilians in the Battle of Stalingrad. The project overcomes the one-sided look at the war generation as to the “chosen” one, having a special part in history; this allows the return to the historic justice in the space of memory. Description of the project work, analysis of problems and prospects of using prosopographic methods in the study of the Battle of Stalingrad are performed by E.V. Ogarkova. Collection of biographical articles, work with sources, selection of fragments of biographies of Stalingradians for publication in the article are performed by A.A. Ogarkov. General editing of the article is carried out by I.O. Tyumentsev

Genomic and Phenotypic Analysis of Multidrug-Resistant <i>Acinetobacter baumannii</i> Clinical Isolates Carrying Different Types of CRISPR/Cas Systems

Acinetobacter baumannii is an opportunistic pathogen being one of the most important causative agents of a wide range of nosocomial infections associated with multidrug resistance and high mortality rate. This study presents a multiparametric and correlation analyses of clinical multidrug-resistant A. baumannii isolates using short- and long-read whole-genome sequencing, which allowed us to reveal specific characteristics of the isolates with different CRISPR/Cas systems. We also compared antibiotic resistance and virulence gene acquisition for the groups of the isolates having functional CRISPR/Cas systems, just CRISPR arrays without cas genes, and without detectable CRISPR spacers. The data include three schemes of molecular typing, phenotypic and genotypic antibiotic resistance determination, as well as phylogenetic analysis of full-length cas gene sequences, predicted prophage sequences and CRISPR array type determination. For the first time the differences between the isolates carrying Type I-F1 and Type I-F2 CRISPR/Cas systems were investigated. A. baumannii isolates with Type I-F1 system were shown to have smaller number of reliably detected CRISPR arrays, and thus they could more easily adapt to environmental conditions through acquisition of antibiotic resistance genes, while Type I-F2 A. baumannii might have stronger “immunity” and use CRISPR/Cas system to block the dissemination of these genes. In addition, virulence factors abaI, abaR, bap and bauA were overrepresented in A. baumannii isolates lacking CRISPR/Cas system. This indicates the role of CRISPR/Cas in fighting against phage infections and preventing horizontal gene transfer. We believe that the data presented will contribute to further investigations in the field of antimicrobial resistance and CRISPR/Cas studies

Comparative Whole-Genome Analysis of Russian Foodborne Multidrug-Resistant Salmonella Infantis Isolates

Non-typhoidal Salmonella infections remain a significant public health problem worldwide. In this study, we present the first detailed genomic analysis report based on short-read (Illumina) whole-genome sequencing (WGS) of 45 multidrug-resistant (MDR) Salmonella enterica subsp. enterica serotype Infantis isolates from poultry and meat product samples obtained in Russia during 2018&ndash;2020, and long-read (MinION) WGS of five more representative isolates. We sought to determine whether foodborne S. Infantis have acquired new characteristics, traits, and dynamics in MDR growth in recent years. All sequenced isolates belonged to the sequence type ST32 and more than the half of isolates was characterized by six similar antimicrobial susceptibility profiles, most of which corresponded well with the antimicrobial resistance determinants to aminoglycosides, sulphonamides, tetracycline, and chloramphenicol revealed in silico. Some of the isolates were characterized by the presence of several types of plasmids simultaneously. Plasmid typing using WGS revealed Col440I, ColpVC, ColRNAI, IncFIB, IncFII, IncX1, IncHI2, IncHI2A, and IncN replicons. The identified virulence genes for 45 whole genomes of S. Infantis were similar and included 129 genes encoding structural components of the cell, factors responsible for successful invasion of the host, and secreted products. These data will be a valuable contribution to further comparative genomics of S. Infantis circulating in Russia, as well as to epidemiological surveillance of foodborne Salmonella isolates and investigations of Salmonella outbreaks