Antiviral Susceptibility of Swine-Origin Influenza A Viruses Isolated from Humans, United States.

Autor: Gao R, Pascua PNQ, Chesnokov A, Nguyen HT, Uyeki TM, Mishin VP, Zanders N, Cui D, Jang Y, Jones J, La Cruz J, Di H, Davis CT, Gubareva LV
Jazyk: angličtina
Zdroj: Emerging infectious diseases [Emerg Infect Dis] 2024 Nov; Vol. 30 (11), pp. 2303-2312. Date of Electronic Publication: 2024 Oct 08.
DOI: 10.3201/eid3011.240892
Abstrakt: 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.
Databáze: MEDLINE