High-throughput profiling of influenza A virus hemagglutinin gene at single-nucleotide resolution

Nicholas C. Wu, Arthur P. Young, Laith Q. Al-Mawsawi, C. Anders Olson, Jun Feng, Hangfei Qi, Shu Hwa Chen, I. Hsuan Lu, Chung Yen Lin, Robert G. Chin, Harding H. Luan, Nguyen Nguyen, Stanley F. Nelson, Xinmin Li, Ting Ting Wu, Ren Sun

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Abstract

Genetic research on influenza virus biology has been informed in large part by nucleotide variants present in seasonal or pandemic samples, or individual mutants generated in the laboratory, leaving a substantial part of the genome uncharacterized. Here, we have developed a single-nucleotide resolution genetic approach to interrogate the fitness effect of point mutations in 98% of the amino acid positions in the influenza A virus hemagglutinin (HA) gene. Our HA fitness map provides a reference to identify indispensable regions to aid in drug and vaccine design as targeting these regions will increase the genetic barrier for the emergence of escape mutations. This study offers a new platform for studying genome dynamics, structure-function relationships, virus-host interactions, and can further rational drug and vaccine design. Our approach can also be applied to any virus that can be genetically manipulated.

Original languageEnglish
Article number4942
JournalScientific Reports
Volume4
DOIs
Publication statusPublished - May 13 2014
Externally publishedYes

ASJC Scopus subject areas

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    Wu, N. C., Young, A. P., Al-Mawsawi, L. Q., Olson, C. A., Feng, J., Qi, H., Chen, S. H., Lu, I. H., Lin, C. Y., Chin, R. G., Luan, H. H., Nguyen, N., Nelson, S. F., Li, X., Wu, T. T., & Sun, R. (2014). High-throughput profiling of influenza A virus hemagglutinin gene at single-nucleotide resolution. Scientific Reports, 4, [4942]. https://doi.org/10.1038/srep04942