ИСТИНА

Oncolytic viruses belong to the new class of antitumor therapy for treatment of aggressive malignant neoplasms. Viral tropism is determined by virion internalization efficiency, depending on the presence of specific receptors and cofactors on cell surface. Oncolytic Echovirus 1 (strain Farouk, E1-F) uses neonatal Fc receptor (FCGRT) for entry into cells. This receptor acts as a pocket factor for virus uncoating, and there are no Enterovirus B strains capable of effective cell infection with no expression of this protein. Using the bioselection method, we had received a derivative strain from canonical E1-F on HEK293T cells with knockout of FCGRT gene. This strain can effectively replicate on HEK293T ΔFCGRT cells. Over the course of genome sequence analysis, we had detected a significant number of non-synonymous substitutions in structural segment of new strain polypeptide. Amino acid sequence analysis of structural proteins interacting with FCGRT indicates changes in intrinsically disordered protein regions (IDPRs) positions. The emergence of these regions may have led to a change in the new strain tropism to the already known cellular factors. Assessment of tropism of the new strain to tumor cell lines showed a significant change in comparison with the original strain. In vitro experiments demonstrated the oncolytic potential was preserved. Further study of IDPRs positions in structural proteins can shed some light on the process of virus host change.