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Neuraminidase Inhibitor Susceptibility Testing in Human Influenza Viruses: A Laboratory Surveillance Perspective
Virus Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop G16, Atlanta, GA 30333, USA
Atlanta Research and Education Foundation, 1670 Clairmont Rd, 151F, Decatur, GA 30033, USA
Battelle, Century Plaza 1, 2987 Clairmont Rd, Suite 450, Atlanta, GA 30329, USA
Oak Ridge Institute for Science and Education, MC-100-22, P.O. Box 117, Oak Ridge, TN 37831, USA
Influenza and Respiratory Viruses Section, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington St., Suite H4050, Winnipeg, MB, R3E 3R2, Canada
* Author to whom correspondence should be addressed.
Received: 30 August 2010; in revised form: 5 October 2010 / Accepted: 7 October 2010 / Published: 13 October 2010
Abstract: Neuraminidase inhibitors (NAIs) are vital in managing seasonal and pandemic influenza infections. NAI susceptibilities of virus isolates (n = 5540) collected during the 2008–2009 influenza season were assessed in the chemiluminescent neuraminidase inhibition (NI) assay. Box-and-whisker plot analyses of log-transformed IC50s were performed for each virus type/subtype and NAI to identify outliers which were characterized based on a statistical cutoff of IC50 >3 interquartile ranges (IQR) from the 75th percentile. Among 1533 seasonal H1N1 viruses tested, 1431 (93.3%) were outliers for oseltamivir; they all harbored the H275Y mutation in the neuraminidase (NA) and were reported as oseltamivir-resistant. Only 15 (0.7%) of pandemic 2009 H1N1 viruses tested (n = 2259) were resistant to oseltamivir. All influenza A(H3N2) (n = 834) and B (n = 914) viruses were sensitive to oseltamivir, except for one A(H3N2) and one B virus, with D151V and D197E (D198E in N2 numbering) mutations in the NA, respectively. All viruses tested were sensitive to zanamivir, except for six seasonal A(H1N1) and several A(H3N2) outliers (n = 22) which exhibited cell culture induced mutations at residue D151 of the NA. A subset of viruses (n = 1058) tested for peramivir were sensitive to the drug, with exception of H275Y variants that exhibited reduced susceptibility to this NAI. This study summarizes baseline susceptibility patterns of seasonal and pandemic influenza viruses, and seeks to contribute towards criteria for defining NAI resistance.
Keywords: Oseltamivir; zanamivir; peramivir; seasonal influenza A and B; pandemic H1N1
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MDPI and ACS Style
Okomo-Adhiambo, M.; Sleeman, K.; Ballenger, K.; Nguyen, H.T.; Mishin, V.P.; Sheu, T.G.; Smagala, J.; Li, Y.; Klimov, A.I.; Gubareva, L.V. Neuraminidase Inhibitor Susceptibility Testing in Human Influenza Viruses: A Laboratory Surveillance Perspective. Viruses 2010, 2, 2269-2289.
Okomo-Adhiambo M, Sleeman K, Ballenger K, Nguyen HT, Mishin VP, Sheu TG, Smagala J, Li Y, Klimov AI, Gubareva LV. Neuraminidase Inhibitor Susceptibility Testing in Human Influenza Viruses: A Laboratory Surveillance Perspective. Viruses. 2010; 2(10):2269-2289.
Okomo-Adhiambo, Margaret; Sleeman, Katrina; Ballenger, Kristina; Nguyen, Ha T.; Mishin, Vasiliy P.; Sheu, Tiffany G.; Smagala, James; Li, Yan; Klimov, Alexander I.; Gubareva, Larisa V. 2010. "Neuraminidase Inhibitor Susceptibility Testing in Human Influenza Viruses: A Laboratory Surveillance Perspective." Viruses 2, no. 10: 2269-2289.