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

doi:10.1038/srep04942

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

Research output: Contribution to journal › Article › peer-review

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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 language	English
Article number	4942
Journal	Scientific Reports
Volume	4
DOIs	https://doi.org/10.1038/srep04942
Publication status	Published - May 13 2014
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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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, Article 4942. https://doi.org/10.1038/srep04942

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title = "High-throughput profiling of influenza A virus hemagglutinin gene at single-nucleotide resolution",

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.",

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

note = "Funding Information: We would like to thank J. Zhou, J. Yoshizawa, T. Toy and Z. Chen for performing the high-throughput sequencing experiment. This work was supported by the National Institute of Health (reference R01-EB-009764), UCLA Molecular Biology Whitcome Pre-Doctoral Fellowship, Oppenheimer Endowment Awards and Clinical Translational Seed Grants, and the UCLA Jonsson Comprehensive Cancer Center.",

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doi = "10.1038/srep04942",

language = "English",

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T1 - High-throughput profiling of influenza A virus hemagglutinin gene at single-nucleotide resolution

AU - Wu, Nicholas C.

AU - Young, Arthur P.

AU - Al-Mawsawi, Laith Q.

AU - Olson, C. Anders

AU - Feng, Jun

AU - Qi, Hangfei

AU - Chen, Shu Hwa

AU - Lu, I. Hsuan

AU - Lin, Chung Yen

AU - Chin, Robert G.

AU - Luan, Harding H.

AU - Nguyen, Nguyen

AU - Nelson, Stanley F.

AU - Li, Xinmin

AU - Wu, Ting Ting

AU - Sun, Ren

N1 - Funding Information: We would like to thank J. Zhou, J. Yoshizawa, T. Toy and Z. Chen for performing the high-throughput sequencing experiment. This work was supported by the National Institute of Health (reference R01-EB-009764), UCLA Molecular Biology Whitcome Pre-Doctoral Fellowship, Oppenheimer Endowment Awards and Clinical Translational Seed Grants, and the UCLA Jonsson Comprehensive Cancer Center.

PY - 2014/5/13

Y1 - 2014/5/13

N2 - 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.

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

Abstract

ASJC Scopus subject areas

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