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

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

Author information

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.

PMID:
24820965
PMCID:
PMC4018626
DOI:
10.1038/srep04942
[Indexed for MEDLINE]
Free PMC Article

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