1. Antiviral Susceptibility of Swine-Origin Influenza A Viruses Isolated from Humans, United States
- Author
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Rongyuan Gao, Philippe Noriel Q. Pascua, Anton Chesnokov, Ha T. Nguyen, Timothy M. Uyeki, Vasiliy P. Mishin, Natosha Zanders, Dan Cui, Yunho Jang, Joyce Jones, Juan De La Cruz, Han Di, Charles Todd Davis, and Larisa V. Gubareva
- Subjects
influenza ,viruses ,swine-origin influenza A virus ,human infections ,antivirals ,baloxavir marboxil ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Since 2013, a total of 167 human infections with swine-origin (variant) influenza A viruses of A(H1N1)v, A(H1N2)v, and A(H3N2)v subtypes have been reported in the United States. Analysis of 147 genome sequences revealed that nearly all had S31N substitution, an M2 channel blocker-resistance marker, whereas neuraminidase inhibitor–resistance markers were not found. Two viruses had a polymerase acidic substitution (I38M or E199G) associated with decreased susceptibility to baloxavir, an inhibitor of viral cap-dependent endonuclease (CEN). Using phenotypic assays, we established subtype-specific susceptibility baselines for neuraminidase and CEN inhibitors. When compared with either baseline or CEN-sequence–matched controls, only the I38M substitution decreased baloxavir susceptibility, by 27-fold. Human monoclonal antibodies FI6v3 and CR9114 targeting the hemagglutinin’s stem showed variable (0.03 to >10 µg/mL) neutralizing activity toward variant viruses, even within the same clade. Methodology and interpretation of laboratory data described in this study provide information for risk assessment and decision-making on therapeutic control measures.
- Published
- 2024
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