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Virology Journal
Published in: Virology Journal 1/2013

Open Access 01-12-2013 | Research

Genetic diversity among pandemic 2009 influenza viruses isolated from a transmission chain

Authors: Sarah L Fordyce, Karoline Bragstad, Svend Stenvang Pedersen, Thøger G Jensen, Bente Gahrn-Hansen, Rod Daniels, Alan Hay, Marie-Louise Kampmann, Christian AW Bruhn, J Victor Moreno-Mayar, María C Ávila-Arcos, M Thomas P Gilbert, Lars P Nielsen

Published in: Virology Journal | Issue 1/2013

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Abstract

Background

Influenza viruses such as swine-origin influenza A(H1N1) virus (A(H1N1)pdm09) generate genetic diversity due to the high error rate of their RNA polymerase, often resulting in mixed genotype populations (intra-host variants) within a single infection. This variation helps influenza to rapidly respond to selection pressures, such as those imposed by the immunological host response and antiviral therapy. We have applied deep sequencing to characterize influenza intra-host variation in a transmission chain consisting of three cases due to oseltamivir-sensitive viruses, and one derived oseltamivir-resistant case.

Methods

Following detection of the A(H1N1)pdm09 infections, we deep-sequenced the complete NA gene from two of the oseltamivir-sensitive virus-infected cases, and all eight gene segments of the viruses causing the remaining two cases.

Results

No evidence for the resistance-causing mutation (resulting in NA H275Y substitution) was observed in the oseltamivir-sensitive cases. Furthermore, deep sequencing revealed a subpopulation of oseltamivir-sensitive viruses in the case carrying resistant viruses. We detected higher levels of intra-host variation in the case carrying oseltamivir-resistant viruses than in those infected with oseltamivir-sensitive viruses.

Conclusions

Oseltamivir-resistance was only detected after prophylaxis with oseltamivir, suggesting that the mutation was selected for as a result of antiviral intervention. The persisting oseltamivir-sensitive virus population in the case carrying resistant viruses suggests either that a small proportion survive the treatment, or that the oseltamivir-sensitive virus rapidly re-establishes itself in the virus population after the bottleneck. Moreover, the increased intra-host variation in the oseltamivir-resistant case is consistent with the hypothesis that the population diversity of a RNA virus can increase rapidly following a population bottleneck.
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Metadata
Title
Genetic diversity among pandemic 2009 influenza viruses isolated from a transmission chain
Authors
Sarah L Fordyce
Karoline Bragstad
Svend Stenvang Pedersen
Thøger G Jensen
Bente Gahrn-Hansen
Rod Daniels
Alan Hay
Marie-Louise Kampmann
Christian AW Bruhn
J Victor Moreno-Mayar
María C Ávila-Arcos
M Thomas P Gilbert
Lars P Nielsen
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2013
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-10-116

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