Antiviral Resistance in Influenza Viruses Jennifer Laplante, BS, Kirsten St. George, MAppSc, PhD  Clinics in Laboratory Medicine  Volume 34, Issue 2, Pages 387-408 (June 2014) DOI: 10.1016/j.cll.2014.02.010 Copyright © 2014 Elsevier Inc. Terms and Conditions

Fig. 1 Schematic representations of the influenza matrix and NA genes of influenza A/H1N1pdm09, A/H3N2, and influenza B. Amino acid positions within each gene whereby changes are associated with antiviral resistance are indicated. Standard N2 numbering is used throughout. a Variants with both the Q313K and the I427T changes are resistant to oseltamivir and zanamivir.99 b The I222L change alone does not alter antiviral susceptibility; however, in combination with E119V it results in extreme resistance to oseltamivir.21 Figure generated with Geneious, version 5.4.6, created by Biomatters. Available from http://www.geneious.com/. Clinics in Laboratory Medicine 2014 34, 387-408DOI: (10.1016/j.cll.2014.02.010) Copyright © 2014 Elsevier Inc. Terms and Conditions

Fig. 2 The structures of influenza A/H1pdm09 and A/Tanzania/205/2010(H3N2) NA enzymes (on left and right, respectively), PDB codes 3TI6122 and 4GZT,123 outlined as ribbon diagrams and colored according to amino acid position (from blue, N-terminus, to red, C-terminus). Amino acid substitutions that are known to impact influenza antiviral susceptibility for zanamivir and oseltamivir are shown as sticks and translucent spheres. Oseltamivir (black sticks) is shown bound in the active site of the enzyme. Parent side chains are labeled by single letter code and residue number. Mutations Q313K + I427T, which confer dual resistance to oseltamivir and zanamivir, are shown in blue sticks. Images generated with The PyMOL Molecular Graphics System, version 1.1, Schrödinger, LLC. Clinics in Laboratory Medicine 2014 34, 387-408DOI: (10.1016/j.cll.2014.02.010) Copyright © 2014 Elsevier Inc. Terms and Conditions