Abstract
Rapid identification of influenza antigenic variants will be critical in selecting optimal vaccine candidates and thus a key to developing an effective vaccination program. Recent studies suggest that multiple simultaneous mutations at antigenic sites accumulatively enhance antigenic drift of influenza A viruses. However, pre-existing methods on antigenic variant identification are based on analyses from individual sites. Because the impacts of these co-evolved sites on influenza antigenicity may not be additive, it will be critical to quantify the impact of not only those single mutations but also multiple simultaneous mutations or co-evolved sites. Here, we developed and applied a computational method, AntigenCO, to identify and quantify both single and co-evolutionary sites driving the historical antigenic drifts. AntigenCO achieved an accuracy of up to 90.05% for antigenic variant prediction, significantly outperforming methods based on single sites. AntigenCO can be useful in antigenic variant identification in influenza surveillance.
Highlights
Influenza A virus causes both seasonal and pandemic outbreaks, presenting a continuous challenge to public health
This framework was applied into H3N2 influenza dataset containing 512 viruses and 133 serums collected between 1968 and 2007 together with the corresponding HA1 protein, and the obtained prediction model was tested on H3N2 influenza viruses from 2002 to 2013
As influenza A viruses have been evolved into antigenic clusters [5], we applied AntigenCO to infer mutations leading to the antigenic drift events among these clusters
Summary
Influenza A virus causes both seasonal and pandemic outbreaks, presenting a continuous challenge to public health. Influenza A virus is an RNA virus in the family Orthomyxoviridae, and its genome is composed of eight negative stranded RNA segments. Namely antigenic drift and antigenic shift, drive the antigenic changes of influenza A virus. Antigenic drift is mainly caused by mutations in influenza surface glycoproteins hemagglutinin (HA) and neuraminidase (NA), which are primary targets for host immune systems. Antigenic shift occurs when an influenza strain with antigenically distinct HA and/or NA genes appears, usually resulting from genetic reassortment. Genetic reassortment is the exchange of one or more discrete RNA segments into multipartite viruses when two or more viruses infect the same cell. Antigenic drift events occur more frequently than antigenic shift events
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