Antigenic drift and subtype interference shape A(H3N2) epidemic dynamics in the United States.

Antigenic drift and subtype interference shape A(H3N2) epidemic dynamics in the United States.

Publication date: Sep 25, 2024

Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity.

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Concepts Keywords
Annual Adolescent
Epidemiology Adult
Fitness antigenic drift
Genetic Antigens, Viral
Viruses Antigens, Viral
Child
Child, Preschool
Epidemics
epidemiology
Evolution, Molecular
global health
H3N2
human
Humans
infectious disease
influenza virus
Influenza, Human
microbiology
Middle Aged
Neuraminidase
Neuraminidase
Seasons
United States
virus
Young Adult

Semantics

Type Source Name
disease MESH Influenza
disease MESH reinfection
disease IDO process
pathway KEGG Influenza A
disease IDO susceptibility
disease MESH infectious disease
pathway REACTOME Infectious disease
drug DRUGBANK Influenza A virus

Original Article

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