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.
authors.affiliation: 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].
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Wu
authors.affiliation: 1] Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA [2].
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Young
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Laith Q
authors.initials: LQ
authors.lastname: Al-Mawsawi
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: C Anders
authors.initials: CA
authors.lastname: Olson
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Hangfei
authors.initials: H
authors.lastname: Qi
authors.affiliation: Institute of Information Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Shu-Hwa
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Institute of Information Science, Academia Sinica, Taipei, Taiwan.
authors.forename: I-Hsuan
authors.initials: IH
authors.lastname: Lu
authors.affiliation: Institute of Information Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Chung-Yen
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Chin
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Harding H
authors.initials: HH
authors.lastname: Luan
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Nguyen
authors.affiliation: 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.
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Nelson
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Ren
authors.initials: R
authors.lastname: Sun
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D013329:Structure-Activity Relationship
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus