Assessing baloxavir susceptibility of influenza viruses circulating in the United States during the 2016/17 and 2017/18 seasons

• Published in: Euro surveillance : bulletin européen sur les maladies transmissibles Vol. 24; no. 3; p. 1
• Main Authors: Gubareva, Larisa V, Mishin, Vasiliy P, Patel, Mira C, Chesnokov, Anton, Nguyen, Ha T, De La Cruz, Juan, Spencer, Sarah, Campbell, Angela P, Sinner, Mallory, Reid, Heather, Garten, Rebecca, Katz, Jackie M, Fry, Alicia M, Barnes, John, Wentworth, David E
• Format: Journal Article
• Language: English
• Published: Sweden Centre Europeen pour la Surveillance Epidemiologique du SIDA (European Centre for the Epidemiological Monitoring of AIDS) 17.01.2019; European Centre for Disease Prevention and Control (ECDC)
• Subjects: Amino Acid Substitution - drug effects; Amino Acid Substitution - genetics; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Dibenzothiepins; Drug Resistance, Viral - genetics; Drug therapy; Enzyme Inhibitors - pharmacology; Humans; Immunization; Influenza; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H3N2 Subtype - drug effects; Influenza A Virus, H3N2 Subtype - genetics; Influenza A Virus, H3N2 Subtype - isolation & purification; Influenza B virus - drug effects; Influenza B virus - genetics; Influenza B virus - isolation & purification; Influenza, Human - drug therapy; Influenza, Human - epidemiology; Influenza, Human - virology; Microbial Sensitivity Tests; Morpholines; Oxazines - pharmacology; Pyridines - pharmacology; Pyridones; Rapid Communication; Seasons; Sentinel Surveillance; Thiepins - pharmacology; Triazines - pharmacology; United States; Viral Proteins - genetics; Viruses; United States; United States > US; influenza; Cap-dependent endonuclease inhibitor; influenza surveillance; polymerase acidic protein; next generation sequencing; drug resistance; phenotypic testing
• ISSN: 1560-7917; 1025-496X; 1560-7917
• DOI: 10.2807/1560-7917.es.2019.24.3.1800666

The anti-influenza therapeutic baloxavir targets cap-dependent endonuclease activity of polymerase acidic (PA) protein. We monitored baloxavir susceptibility in the United States with next generation sequencing analysis supplemented by phenotypic one-cycle infection assay. Analysis of PA sequences of 6,891 influenza A and B viruses collected during 2016/17 and 2017/18 seasons showed amino acid substitutions: I38L (two A(H1N1)pdm09 viruses), E23G (two A(H1N1)pdm09 viruses) and I38M (one A(H3N2) virus); conferring 4-10-fold reduced susceptibility to baloxavir.