Genetic Changes in Influenza a Virus Genes Responsible for Formation of Drug Resistance Phenotype

Abstract

Here we present the results of adaptation and analysis of genetic changes of influenza strains A/FPV/Waybrige/78 (H7N7) and A/Swine/Iowa/30 (H1N1) to blockers of ion channels (Remantadin®) and neuraminidase inhibitor (Tamiflu®). From 6 to 10 times increase in the IC50 value of Tamiflu for FPV_RTam and Sw_RTam compared with wild-type variants was shown. The IC50 value was increased by 10 to 33 times for Remantadin-resistant mutants. The substitutions S31N and A30T were shown in the M2 protein structure of mutants FPV_RRim and Sw_RRim respectively. The mutations like H274Y in the structure of neuraminidase which are responsible for resistance to Tamiflu, in the mutants FPV_RTam and Sw_RTam was not revealed. But, in the structure of the M1 protein amino acid sequence of these mutants, an unexpected substitution at position 207 was recorded. To study the problems of formation of drug-resistant viruses and find the ways to overcome the resistance, the experiments were carried out on the adaptation of influenza virus strains to high concentrations of antiviral drugs.