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Rodney S. Daniels

Publications and source records attributed to Rodney S. Daniels.

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Prediction, dynamics, and visualization of antigenic phenotypes of seasonal influenza viruses

Human seasonal influenza viruses evolve rapidly, enabling the virus population to evade immunity and re-infect previously infected individuals. Antigenic properties are largely determined by the surface glycoprotein hemagglutinin (HA) and amino acid substitutions at exposed epitope sites in HA mediate loss of recognition by antibodies. Here, we show that antigenic differences measured through serological assay data are well described by a sum of antigenic changes along the path connecting viruses in a phylogenetic tree. This mapping onto the tree allows prediction of antigenicity from HA sequence data alone. The mapping can further be used to make predictions about the makeup of the future seasonal influenza virus population, and we compare predictions between models with serological and sequence data. To make timely model output readily available, we developed a web browser based application that visualizes antigenic data on a continuously updated phylogeny.

q-bio.PE

Identifying the genetic basis of antigenic change in influenza A(H1N1)

Determining phenotype from genetic data is a fundamental challenge. Influenza A viruses undergo rapid antigenic drift and identification of emerging antigenic variants is critical to the vaccine selection process. Using former seasonal influenza A(H1N1) viruses, hemagglutinin sequence and corresponding antigenic data were analyzed in combination with 3-D structural information. We attributed variation in hemagglutination inhibition to individual amino acid substitutions and quantified their antigenic impact, validating a subset experimentally using reverse genetics. Substitutions identified as low-impact were shown to be a critical component of influenza antigenic evolution and by including these, as well as the high-impact substitutions often focused on, the accuracy of predicting antigenic phenotypes of emerging viruses from genotype was doubled. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine techniques that predict the fitness and evolutionary success of variant viruses, leading to stronger theoretical foundations for selection of candidate vaccine viruses.

q-bio.PE