The 3C protease is a key factor in picornavirus-induced pathologies with a comprehensive action on cell targets. However, the effects induced by the enzyme have not been described at the organismic level. Here, the model of developing Danio rerio embryos was used to analyze possible toxic effects of the 3C protease of human hepatitis A virus (3Cpro) at the whole-body level. The transient 3Cpro expression had a notable lethal effect and induced a number of specific abnormalities in Danio rerio embryos within 24 h. These effects are due to the proteolytic activity of the enzyme. At the same time, the 3Cpro variant with reduced catalytic activity (3Cmut) increased the incidence of embryonic abnormalities; however, this effect was smaller compared to the native enzyme form. While the expression of 3Cmut increased the overall rate of abnormalities, no predominance of specific ones was observed. The data obtained point to a presence significant impact of picornavirus 3Cprotease at the whole-organism level and make contribution to the study of the infectious process caused by human hepatitis A virus.

Embryonal malignant tumors of the central nervous system present a serious threat to the lives of children, making the search for new therapeutic strategie

The identification of tissue-specific promoters for gene therapeutic constructs is one of the aims of complex tumor therapy. The genes encoding the fibroblast activation protein (FAP) and the connective tissue growth factor (CTGF) can function in tumor-associated stromal cells but are practically inactive in normal adult cells. Accordingly, the promoters of these genes can be used to develop vectors targeted to the tumor microenvironment. However, the efficiency of these promoters within genetic constructs remains underexplored, particularly, at the organism level. Here, we used the model of Danio rerio embryos to study the efficiency of transient expression of marker genes under the control of promoters of the FAP, CTGF, and immediate early genes of Human cytomegalovirus (CMV). Within 96 h after the injection of vectors, the CTGF and CMV promoters provided similar equal efficiency of reporter protein accumulation. In the case of the FAP promoter, a high level of reporter protein accumulation was observed only in certain zebrafish individuals that were considered developmentally abnormal. Disturbed embryogenesis was the factor of changes in the exogenous FAP promoter function. The data obtained make a significant contribution to understanding the function of the human CTGF and FAP promoters within vectors to assess their potential in gene therapy.

Embryonal malignant tumors of the central nervous system present a serious threat to the lives of children, making the search for new therapeutic strategies in this area of pediatric medicine highly relevant. The development of new experimental approaches for biomedical research, including the creation of model systems, is particularly important. Recently, the teleost freshwater fish Danio rerio has gained popularity as an alternative to widely used mammalian models due to its ease of breeding, rapid extrauterine development and embryonic transparency. These characteristics make D. rerio fish extremely useful for studying tumor initiation, progression and metastasis, as well as for in vivo drug screening, which is essential for the successful development of personalized medicine. This review describes transplantation approaches to modeling embryonal tumors of the central nervous system using D. rerio. Both xenogenic and syngeneic transplantation models are considered, the use of which will help study the biology of the central nervous system embryonal tumors and create the organism test systems for antitumor drug search.