Next Article in Journal
Antiviral Effects of Black Raspberry (Rubus coreanus) Seed and Its Gallic Acid against Influenza Virus Infection
Next Article in Special Issue
Vesicular Nucleo-Cytoplasmic Transport—Herpesviruses as Pioneers in Cell Biology
Previous Article in Journal
The Role of microRNAs in the Pathogenesis of Herpesvirus Infection
Article Menu

Export Article

Open AccessArticle
Viruses 2016, 8(6), 155; doi:10.3390/v8060155

Accurate Measurement of the Effects of All Amino-Acid Mutations on Influenza Hemagglutinin

1
Division of Basic Sciences Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA
2
Department of Genome Sciences, University of Washington, 3720 15th Ave NE, Seattle, WA 98195-5065, USA
3
Medical Scientist Training Program, University of Washington, Seattle, WA 98109, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Eric O. Freed and Thomas Klimkait
Received: 23 April 2016 / Revised: 21 May 2016 / Accepted: 25 May 2016 / Published: 3 June 2016
(This article belongs to the Special Issue Viruses 2016 - At the Forefront of Virus-Host Interactions)
View Full-Text   |   Download PDF [7967 KB, uploaded 7 June 2016]   |  

Abstract

Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution. View Full-Text
Keywords: influenza; hemagglutinin; mutational tolerance; deep mutational scanning; evolution influenza; hemagglutinin; mutational tolerance; deep mutational scanning; evolution
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary materials

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Doud, M.B.; Bloom, J.D. Accurate Measurement of the Effects of All Amino-Acid Mutations on Influenza Hemagglutinin. Viruses 2016, 8, 155.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top