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

Sci Rep. 2014 May 13:4:4942. doi: 10.1038/srep04942.

Authors

Nicholas C Wu¹, Arthur P Young², Laith Q Al-Mawsawi³, C Anders Olson³, Jun Feng³, Hangfei Qi³, Shu-Hwa Chen⁴, I-Hsuan Lu⁴, Chung-Yen Lin⁴, Robert G Chin⁵, Harding H Luan³, Nguyen Nguyen³, Stanley F Nelson⁶, Xinmin Li⁷, Ting-Ting Wu³, Ren Sun⁸

Affiliations

¹ 1] Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA [2] Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA [3].
² 1] Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA [2].
³ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
⁴ Institute of Information Science, Academia Sinica, Taipei, Taiwan.
⁵ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
⁶ 1] Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA [2] Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
⁷ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
⁸ 1] Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA [2] Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA [3] AIDS Institute, University of California, Los Angeles, CA 90095, USA.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Cell Line
Hemagglutinin Glycoproteins, Influenza Virus / chemistry
Hemagglutinin Glycoproteins, Influenza Virus / genetics*
High-Throughput Nucleotide Sequencing*
Humans
Influenza A Virus, H1N1 Subtype / genetics*
Models, Molecular
Mutation
Phenotype
Polymorphism, Single Nucleotide*
Protein Conformation
Protein Interaction Domains and Motifs
Structure-Activity Relationship

Substances

Hemagglutinin Glycoproteins, Influenza Virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding