Journal Article

Selection of Influenza A and B Viruses for Resistance to 4-Guanidino-Neu5Ac2en in Cell Culture

Joseph M. Colacino, W. Graeme Laver and Gillian M. Air

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 176, issue Supplement_1, pages S66-S68
Published in print August 1997 | ISSN: 0022-1899
Published online August 1997 | e-ISSN: 1537-6613 | DOI: https://dx.doi.org/10.1086/514179
Selection of Influenza A and B Viruses for Resistance to 4-Guanidino-Neu5Ac2en in Cell Culture

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The reassortant influenza viruses, A/NWS-G70c with N9 neuraminidase (NA) and B/HK/8/73 (HG) with B/Lee/40 NA, were selected for resistance to 4-guanidino-Neu5Ac2en (4-GuDANA) by passaging the virus in stepwise increases in the concentration of 4-GuDANA. In the NA of resistant viruses, the absolutely conserved Glu 119, which lies in a pocket beneath the active site of the enzyme and interacts with the guanidinium moiety of 4-GuDANA, was changed to Gly. The mutant NA was < 200-fold more resistant to 4-GuDANA than was the wild-type enzyme. During 72 h in cell culture, resistant A and B viruses displayed much less NA activity than did wild-type viruses but did undergo multicycle replication. While emergence of resistance to 4-GuDANA has not been observed in vivo, these results demonstrate that the development of resistance is possible and can be mediated by a single amino acid change in the active site of the viral NA.

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Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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