Ancient evolutionary origins of hepatitis E virus in rodents.

Hepatitis E virus (HEV; family ) infections cause >40,000 human deaths annually. Zoonotic infections predominantly originate from ungulates and occasionally from rats, highlighting the zoonotic potential of rodent-associated hepeviruses. We conducted host genomic data mining and uncovered two genetically divergent rodent-associated hepeviruses, and two bat-associated hepeviruses genetically related to known bat-associated strains.

Dissimilar local risk factors among patients diagnosed with cystic echinococcosis upon voluntary screening in highly endemic regions of Kyrgyz Republic.

Echinococcosis is a parasitic invasion caused by a cestode of the genus . Kyrgyzstan is a country in Central Asia known for an extremely high incidence of echinococcosis. A total of 10 093 subjects were screened in the Osh, Naryn and Batken regions of Kyrgyzstan in 2015–2017 by ultrasound and questioned for potential risk factors.

Clinical and Translational Landscape of Viral Gene Therapies.

Gene therapies hold significant promise for treating previously incurable diseases. A number of gene therapies have already been approved for clinical use. Currently, gene therapies are mostly limited to the use of adeno-associated viruses and the herpes virus.

Selection Pressure Profile Suggests Species Criteria among Tick-Borne Orthoflaviviruses.

Orthoflaviviruses are arthropod-borne viruses that are transmitted by mosquitoes or ticks and cause a range of significant human diseases. Among the most important tick-borne orthoflaviviruses (TBFVs) is tick-borne encephalitis virus (TBEV), which is endemic in Eurasia, and Powassan virus, which is endemic in Asia and North America. There is a significant controversy regarding species assignment in the tick-borne encephalitis virus complex due to the complex phylogenetic, serological, ecological, and pathogenetic properties of viruses.

Saponin is Essential for the Isolation of Proteins and RNA from Biological Nanoparticles.

Extracellular vesicles (EVs), biomimetics, and other biological nanoparticles (BNs) produced from human cells are gaining increasing attention in the fields of molecular diagnostics and nanomedicine for the delivery of therapeutic cargo. In particular, BNs are considered prospective delivery vehicles for different biologics, including protein and RNA therapeutics. Moreover, EVs are widely used in molecular diagnostics for early detection of disease-associated proteins and RNA.

Phenotypic assessment of antiviral activity for spiro-annulated oxepanes and azepenes.

Evolutionary potential of viruses can result in outbreaks of well-known viruses and emergence of novel ones. Pharmacological methods of intervening the reproduction of various less popular, but not less important viruses are not available, as well as the spectrum of antiviral activity for most known compounds. In the framework of chemical biology paradigm, characterization of antiviral activity spectrum of new compounds allows to extend the antiviral chemical space and provides new important structure-activity relationships for data-driven drug discovery.

mA Methylation in Regulation of Antiviral Innate Immunity.

The epitranscriptomic modification mA is a prevalent RNA modification that plays a crucial role in the regulation of various aspects of RNA metabolism. It has been found to be involved in a wide range of physiological processes and disease states. Of particular interest is the role of mA machinery and modifications in viral infections, serving as an evolutionary marker for distinguishing between self and non-self entities.

The menace of severe adverse events and deaths associated with viral gene therapy and its potential solution.

Over the past decade, in vivo gene replacement therapy has significantly advanced, resulting in market approval of numerous therapeutics predominantly relying on adeno-associated viral vectors (AAV). While viral vectors have undeniably addressed several critical healthcare challenges, their clinical application has unveiled a range of limitations and safety concerns. This review highlights the emerging challenges in the field of gene therapy.

Non-Polio Enteroviruses Isolated by Acute Flaccid Paralysis Surveillance Laboratories in the Russian Federation in 1998-2021: Distinct Epidemiological Features of Types.

More than 100 types of non-polio enteroviruses (NPEVs) are ubiquitous in the human population and cause a variety of symptoms ranging from very mild to meningitis and acute flaccid paralysis (AFP). Much of the information regarding diverse pathogenic properties of NPEVs comes from the surveillance of poliovirus, which also yields NPEV. The analysis of 265 NPEV isolations from 10,433 AFP cases over 24 years of surveillance and more than 2500 NPEV findings in patients without severe neurological lesions suggests that types EV-A71, E13, and E25 were significantly associated with AFP.

Transient and tunable CRISPRa regulation of APOBEC/AID genes for targeting hepatitis B virus.

APOBEC/AID cytidine deaminases play an important role in innate immunity and antiviral defenses and were shown to suppress hepatitis B virus (HBV) replication by deaminating and destroying the major form of HBV genome, covalently closed circular DNA (cccDNA), without toxicity to the infected cells. However, developing anti-HBV therapeutics based on APOBEC/AID is complicated by the lack of tools for activating and controlling their expression. Here, we developed a CRISPR-activation-based approach (CRISPRa) to induce APOBEC/AID transient overexpression (>4-800,000-fold increase in mRNA levels).

Genomic analysis of Leishmania turanica strains from different regions of Central Asia.

The evolution in Leishmania is governed by the opposite forces of clonality and sexual reproduction, with vicariance being an important factor. As such, Leishmania spp. populations may be monospecific or mixed.

Depleting hepatitis B virus relaxed circular DNA is necessary for resolution of infection by CRISPR-Cas9.

CRISPR-Cas9 systems can directly target the hepatitis B virus (HBV) major genomic form, covalently closed circular DNA (cccDNA), for decay and demonstrate remarkable anti-HBV activity. Here, we demonstrate that CRISPR-Cas9-mediated inactivation of HBV cccDNA, frequently regarded as the "holy grail" of viral persistence, is not sufficient for curing infection. Instead, HBV replication rapidly rebounds because of formation of HBV cccDNA from its precursor, HBV relaxed circular DNA (rcDNA).

Patterns and Temporal Dynamics of Natural Recombination in Noroviruses.

Noroviruses infect a wide range of mammals and are the major cause of gastroenteritis in humans. Recombination at the junction of ORF1 encoding nonstructural proteins and ORF2 encoding major capsid protein VP1 is a well-known feature of noroviruses. Using all available complete norovirus sequences, we systematically analyzed patterns of natural recombination in the genus both throughout the genome and across the genogroups.

Hydroxychloroquine Enhances Cytotoxic Properties of Extracellular Vesicles and Extracellular Vesicle-Mimetic Nanovesicles Loaded with Chemotherapeutics.

Because of their high biocompatibility, biological barrier negotiation, and functionalization properties, biological nanoparticles have been actively investigated for many medical applications. Biological nanoparticles, including natural extracellular vesicles (EVs) and synthetic extracellular vesicle-mimetic nanovesicles (EMNVs), represent novel drug delivery vehicles that can accommodate different payloads. In this study, we investigated the physical, biological, and delivery properties of EVs and EMNVs and analyzed their ability to deliver the chemotherapeutic drug doxorubicin.

Technological aspects of manufacturing and analytical control of biological nanoparticles.

Extracellular vesicles (EVs) are cell-derived biological nanoparticles that gained great interest for drug delivery. EVs have numerous advantages compared to synthetic nanoparticles, such as ideal biocompatibility, safety, ability to cross biological barriers and surface modification via genetic or chemical methods. On the other hand, the translation and the study of these carriers resulted difficult, mostly because of significant issues in up-scaling, synthesis and impractical methods of quality control.

Revisiting epidemiology of leishmaniasis in central Asia: lessons learnt.

In this work we reviewed historical and recent data on spp. infection combining data collected in Turkmenistan, Uzbekistan, Kazakhstan, Kyrgyzstan, Iran, China and Mongolia. We specifically focused on a complex of co-existing species (, and ) sharing the same animal reservoirs and vectors.

Robust AAV Genotyping Based on Genetic Distances in Rep Gene That Are Maintained by Ubiquitous Recombination.

Adeno-associated viruses (AAVs) are a convenient tool for gene therapy delivery. According to the current classification, they are divided into the species AAV A and AAV B within the genus Dependoparvovirus. Historically AAVs were also subdivided on the intraspecies level into 13 serotypes, which differ in tissue tropism and targeted gene delivery capacity.

Evaluating the Impact of Anthropogenic Factors on the Dissemination of Contemporary Cosmopolitan, Arctic, and Arctic-like Rabies Viruses.

Rabies is a globally prevalent viral zoonosis that causes 59,000 deaths per year and has important economic consequences. Most virus spread is associated with the migration of its primary hosts. Anthropogenic dissemination, mainly via the transportation of rabid dogs, shaped virus ecology a few hundred years ago and is responsible for several current outbreaks.

Cases of Acute Flaccid Paralysis Associated with Coxsackievirus A2: Findings of a 20-Year Surveillance in the Russian Federation.

Surveillance for acute flaccid paralysis syndrome (AFP) in children under 15 is the backbone of the Global Polio Eradication Initiative. Laboratory examination of stool samples from AFP cases allows the detection of, along with polioviruses, a variety of non-polio enteroviruses (NPEV). The etiological significance of these viruses in the occurrence of AFP cases has been definitively established only for enteroviruses A71 and D68.

Analyses of -LRV Co-Phylogenetic Patterns and Evolutionary Variability of Viral Proteins.

spp. are important pathogens causing a vector-borne disease with a broad range of clinical manifestations from self-healing ulcers to the life-threatening visceral forms. Presence of (LRV) confers survival advantage to these parasites by suppressing anti-leishmanial immunity in the vertebrate host.

The effects of genetic drift and genomic selection on differentiation and local adaptation of the introduced populations of in southern Russia.

Background: Asian tiger mosquito is an arbovirus vector that has spread from its native habitation areal in Southeast Asia throughout North and South Americas, Europe, and Africa. was first detected in the Southern Federal District of the Russian Federation in the subtropical town of Sochi in 2011. In subsequent years, this species has been described in the continental areas with more severe climate and lower winter temperatures.

Modular Evolution of Coronavirus Genomes.

The viral family comprises four genera, termed -, and Recombination events have been described in many coronaviruses infecting humans and other animals. However, formal analysis of the recombination patterns, both in terms of the involved genome regions and the extent of genetic divergence between partners, are scarce. Common methods of recombination detection based on phylogenetic incongruences (e.

Citizen science initiative points at childhood BCG vaccination as a risk factor for COVID-19.

Current results do not provide conclusive evidence on the effect of BCG vaccination on COVID-19 alone or in combination with other factors. To address this limitation, in this study we used a citizen science initiative on the COVID-19 pandemic to collect data worldwide during 2 October 2020-30 October 2020 (1,233 individuals) in a structured way for analysing factors and characteristics of affected individuals in relation to BCG vaccination. For the first time, the results of our study suggested that vaccination with BCG may increase the risk for COVID-19 at certain age, particularly in individuals vaccinated at childhood.

A hepatitis B virus causes chronic infections in equids worldwide.

Preclinical testing of novel therapeutics for chronic hepatitis B (CHB) requires suitable animal models. Equids host homologs of hepatitis C virus (HCV). Because coinfections of hepatitis B virus (HBV) and HCV occur in humans, we screened 2,917 specimens from equids from five continents for HBV.

Detection of the Invasive Mosquito Species () and () on the Southern Coast of the Crimean Peninsula.

Background: The incidence and area of arbovirus infections is increasing around the world. It is largely linked to the spread of the main arbovirus vectors, invasive mosquito of the genus Previously, it has been reported that reemerged in Russia after a 50-year absence. Moreover, in 2011, was registered in the city of Sochi (South Russia, Black Sea coast) for the first time.