Functional characterization of new emerging nfluenza NA variants
Date Issued
2008
Date
2008
Author(s)
Lin, Ching-Yu
Abstract
Influenza virus has caused worldwide pandemic every year. Although influenza vaccine and therapeutic compounds have effectively prevented people from being infected, the appearance of natural variants and drug-resistant viruses have become an important issue. Therefore, in this study, we aimed to characterize the natural variants of neuraminidase (NA) diverse in H3N2 collected at National Taiwan Universityospital in 2007. From January 2007 to October, the NA genes of H3N2 influenza virus strains isolated from Department of Laboratory Medicine, National Taiwan University were sequenced by Dr. Kao’s laboratory. By phylogenetic analysis, these genesequence were separated into two groups – Group I (mainly composed of the virus strains isolated in January and February) and Group II (composed of the virus strains isolated in later time period). Some group-specific amino acid changes were identified at residues 86, 93, 194, 296, 307, 310, 335, 370, 372 and 387. Among these, residue changes at 335/387 and 370/372 are speculated to affect the protein conformation by protein structural prediction. The NA activity of Group I strains is lower than that of Group II strains and small plaque percentage in Group I is higher than that of Group II. To understand whether these genotype variations did correlate with the phenotype changes, reverse genetics was performed to analyze the differences of NA gene from Group I (754) and Group II (4517). Comparison of enzyme activity, and virus growth curve between these two recombinant viruses, we found that Group I virus had lower NA activity, yet similar growth kinetics as compared to Group II virus while both viruses exhibited comparable sensitivity to a compound from NHRI (BPR2P000150) which is not targeted to NA, Group I virus are 3~5 times more resistant to one NA inhibitor, 2-deoxy-2,3-didehydroD-N-acetylneuraminic acid(DANA). Taken together, we speculate that natural variations in NA do exist and some of them may result in phenotypic changes. Further analysis is required to determine the role of specific amino acid change in NA structure and enzyme activity.
Subjects
Influenza virus
neuraminidase
Taiwan
SDGs
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