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Introduction. Infection of cells with encephalomyocarditis virus type 1 (EMCV-1, Cardiovirus A: Picornaviridae) is accompanied by suppression of cellular protein synthesis. The main role in the inhibition of cellular translation is assigned to the L and 2A «security» proteins. The mechanism of the possible influence of the L protein on cellular translation is unknown. There are hypotheses about the mechanism of influence of 2A protein on the efficiency of cap-dependent translation, which are based on interaction with translation factors and ribosome subunits. However, the available experimental data are contradictory, obtained using different approaches, and do not form a unified model of the interaction between the L and 2A proteins and the cellular translation machinery. Aim. To study the role of L and 2A «security» proteins in the suppression of translation of cellular proteins and the efficiency of translation and processing of viral proteins in infected cells. Materials and methods. Mutant variants of EMCV-1 were obtained to study the properties of L and 2A viral proteins: Zfmut, which has a defective L; Δ2A encoding a partially deleted 2A; ZfmutΔ2A containing mutations in both proteins. Translational processes in infected cells were studied by Western-blot and the pulse method of incorporating radioactively labeled amino acids (14C) into newly synthesized proteins, followed by radioautography. Results. The functional inactivation of the 2A protein does not affect the inhibition of cellular protein synthesis. A direct correlation was found between the presence of active L protein and specific inactivation of cellular protein synthesis at an early stage of viral infection. Nonspecific suppression of the translational processes of the infected cell, accompanied by phosphorylation of eIF2α, occurs at the late stage of infection. Partial removal of the 2A protein from the EMCV-1 genome does not affect the development of this process, while inactivation of the L protein accelerates the onset of complete inhibition of protein synthesis. Partial deletion of the 2A disrupts the processing of viral capsid proteins. Suppression of L protein functions leads to a decrease in the efficiency of viral translation. Conclusion. A study of the role of EMCV-1 L and 2A proteins during the translational processes of an infected cell, first performed using infectious viral pathogens lacking active L and 2A proteins in one experiment, showed that 2A protein is not implicated in the inhibition of cellular translation in HeLa cells; L protein seems to play an important role not only in the specific inhibition of cellular translation but also in maintaining the efficient synthesis of viral proteins; 2A protein is involved not only in primary but also in secondary processing of EMCV-1 capsid proteins.

Introduction. Since the development of inactivated polio vaccines, different stages of the production process have been changed and improved. Current production of inactivated polio vaccines based on both wild and attenuated strains includes several technological stages, one of which is the concentration of the virus-containing liquid, which ensures poliovirus concentration, and purification of the virus-containing liquid from a significant part of the ballast components.Research objective is to compare the characteristics of ultrafiltration membranes and select the membranes that provide optimal value of purification and concentration of poliovirus type 1 (Sabin strain).Materials and methods. Laboratory ultrafiltration systems from two manufacturers with 50, 100, and 300 kDa membranes were used for the concentration. Results were evaluated by the content of total protein, which is the main stress for the subsequent purification stages, the value of infectious virus titer in the concentrate, and the content of D-antigen as the target product.Results and discussion. Obtained results demonstrated that the content of the target product (the highest D-antigen content) and purification from impurity proteins (the total protein content in the concentrate) were most optimal when a membrane with a cut-off of 300 kDa was used for concentration. The study also evaluated the real cut-off components by various membranes to determine the composition of the protein load on the target product.Conclusion. In terms of quality of the resulting target product and the manufacturability of the production process, the use of a 300 kDa membrane is the most appropriate when working out the technology for manufacturing inactivated polio vaccine based on Sabin strains of poliovirus and the Vero line as a producing culture.

The unprecedented in recent history global COVID-19 pandemic urged the implementation of all existing vaccine platforms to ensure the availability of the vaccines against COVID-19 to every country in the world. Despite the multitude of high-quality papers describing clinical trials of different vaccine products, basic detailed data on general toxicity, reproductive toxicity, immunogenicity, protective efficacy and durability of immune response in animal models are scarce. Here, we developed a β-propiolactone-inactivated whole virion vaccine CoviVac and assessed its safety, protective efficacy, immunogenicity and stability of the immune response in rodents and non-human primates. The vaccine showed no signs of acute/chronic, reproductive, embryo- and fetotoxicity, or teratogenic effects, as well as no allergenic properties in studied animal species. The vaccine induced stable and robust humoral immune response both in form of specific anti-SARS-CoV-2 IgG and NAbs in mice, Syrian hamsters, and common marmosets. The NAb levels did not decrease significantly over the course of one year. The course of two immunizations protected Syrian hamsters from severe pneumonia upon intranasal challenge with the live virus. Robustness of the vaccine manufacturing process was demonstrated as well. These data encouraged further evaluation of CoviVac in clinical trials.

Understanding the genetic adaptations that occurred as humans migrated out of Africa to higher latitudes helps explain on a population-wide level how UV radiation (UVR) exposure will have varying consequences and benefits in patients of different skin pigmentations. It has been hypothesized that the need for efficient vitamin D synthesis was the primary driver for the skin-lightening process that evolutionarily occurred as humans migrated to higher latitudes. This review analyzes the level of support for the hypothesis that skin lightening occurred to enable adequate vitamin D synthesis in populations that migrated to areas with less UVR. Our literature search supported the hypothesis that through natural selection and intricate genetic adaptations, humans who migrated to areas with lower levels of UVR underwent a skin-lightening process to avoid the consequences of vitamin D deficiency. Our review includes an analysis of migration patterns out of Africa and how these affected pigmentation genes that are found in certain ethnic populations can be used to better understand this critical adaptation process when counseling patients on the need for sun protection. [ABSTRACT FROM AUTHOR]

Abstract The effect of the composition and density of ceramic materials on the electrical conductivity is investigated for solid electrolytes that are sintered from Ce1 − xGdxO2 − δ (x = 0.09–0.31) nanopowders and have a submicron structure (grain size, 0.1–0.3 µm). The powders are prepared through evaporation of a target with a pulsed CO2 laser, followed by magnetic pulsed compaction. The ceramic materials are synthesized at temperatures in the range 1100–1300°C in air. The effect of the composition on the electrical conductivity is studied for the ion-conducting ceramic samples in the density range up to a limiting value (99.8% of the X-ray density). [ABSTRACT FROM AUTHOR]

Abstract The effect of the composition and density of ceramics on the electroconductivity of solid electrolytes Ce1 − xGdxO2 − δ(x = 0.09–0.31) with a submicron (0.1–0.3 µm) grain size, which are prepared from nanosized powders, is investigated. The powders are synthesized by two methods, specifically, by evaporation of a target with the aid of the radiation of a pulsed carbon dioxide laser and by a chemical method of burning. The samples of ceramics are prepared by magnetopulsed or quasi-isostatic (200–500 MPa) pressing and subsequent caking in air at a temperature of 1100–1300°C. It is established that the electroconductivity of the obtained solid electrolytes is higher and the effective activation energy for conduction is considerably lower as compared with analogous electrolytes with a micron grain size. [ABSTRACT FROM AUTHOR]