Effect of the H275Y neuraminidase mutation on viral fitness of oseltamivir-resistant pandemic 2009 and seasonal H1N1 influenza A viruses

2012 ◽  
Author(s):  
Dik-yan, Diana Wong
2012 ◽  
Vol 87 (3) ◽  
pp. 1912-1915 ◽  
Author(s):  
Michael M. Kaminski ◽  
Annette Ohnemus ◽  
Peter Staeheli ◽  
Dennis Rubbenstroth

ABSTRACTResistance of influenza A viruses to neuraminidase inhibitors can arise through mutations in the neuraminidase (NA) gene. We show here that a Q136K mutation in the NA of the 2009 pandemic H1N1 virus confers a high degree of resistance to zanamivir. Resistance is accompanied by reduced numbers of NA molecules in viral particles and reduced intrinsic enzymatic activity of mutant NA. Interestingly, the Q136K mutation strongly impairs viral fitness in the guinea pig transmission model.


Pneumologie ◽  
2014 ◽  
Vol 68 (02) ◽  
Author(s):  
C Tarnow ◽  
G Engels ◽  
A Arendt ◽  
F Schwalm ◽  
H Sediri ◽  
...  

PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0138704 ◽  
Author(s):  
Venkatramana D. Krishna ◽  
Erin Roach ◽  
Nathan A. Zaidman ◽  
Angela Panoskaltsis-Mortari ◽  
Jessica H. Rotschafer ◽  
...  

2018 ◽  
Vol 92 (24) ◽  
Author(s):  
Amélie Chastagner ◽  
Séverine Hervé ◽  
Emilie Bonin ◽  
Stéphane Quéguiner ◽  
Edouard Hirchaud ◽  
...  

ABSTRACT The H1N1 influenza virus responsible for the most recent pandemic in 2009 (H1N1pdm) has spread to swine populations worldwide while it replaced the previous seasonal H1N1 virus in humans. In France, surveillance of swine influenza A viruses in pig herds with respiratory outbreaks led to the detection of 44 H1N1pdm strains between 2009 and 2017, regardless of the season, and findings were not correlated with pig density. From these isolates, 17 whole-genome sequences were obtained, as were 6 additional hemagglutinin (HA)/neuraminidase (NA) sequences, in order to perform spatial and temporal analyses of genetic diversity and to compare evolutionary patterns of H1N1pdm in pigs to patterns for human strains. Following mutation accumulation and fixation over time, phylogenetic analyses revealed for the first time the divergence of a swine-specific genogroup within the H1N1pdm lineage. The divergence is thought to have occurred around 2011, although this was demonstrated only through strains isolated in 2015 to 2016 in the southern half of France. To date, these H1N1pdm swine strains have not been related to any increased virulence in swine herds and have not exhibited any antigenic drift compared to seasonal human strains. However, further monitoring is encouraged, as diverging evolutionary patterns in these two species, i.e., swine and humans, may lead to the emergence of viruses with a potentially higher risk to both animal and human health.IMPORTANCE Pigs are a “mixing vessel” for influenza A viruses (IAVs) because of their ability to be infected by avian and human IAVs and their propensity to facilitate viral genomic reassortment events. Also, as IAVs may evolve differently in swine and humans, pigs can become a reservoir for old human strains against which the human population has become immunologically naive. Thus, viruses from the novel swine-specific H1N1pdm genogroup may continue to diverge from seasonal H1N1pdm strains and/or from other H1N1pdm viruses infecting pigs and lead to the emergence of viruses that would not be covered by human vaccines and/or swine vaccines based on antigens closely related to the original H1N1pdm virus. This discovery confirms the importance of encouraging swine IAV monitoring because H1N1pdm swine viruses could carry an increased risk to both human and swine health in the future as a whole H1N1pdm virus or gene provider in subsequent reassortant viruses.


2019 ◽  
Vol 78 (6) ◽  
pp. 491-503 ◽  
Author(s):  
Xiao Li ◽  
jianglin Chen ◽  
Jingkai Hu ◽  
Xuanjiang Jin ◽  
Shumin Xie ◽  
...  

2018 ◽  
Vol 115 (45) ◽  
pp. 11613-11618 ◽  
Author(s):  
Daniel H. Goldhill ◽  
Aartjan J. W. te Velthuis ◽  
Robert A. Fletcher ◽  
Pinky Langat ◽  
Maria Zambon ◽  
...  

Favipiravir is a broad-spectrum antiviral that has shown promise in treatment of influenza virus infections. While emergence of resistance has been observed for many antiinfluenza drugs, to date, clinical trials and laboratory studies of favipiravir have not yielded resistant viruses. Here we show evolution of resistance to favipiravir in the pandemic H1N1 influenza A virus in a laboratory setting. We found that two mutations were required for robust resistance to favipiravir. We demonstrate that a K229R mutation in motif F of the PB1 subunit of the influenza virus RNA-dependent RNA polymerase (RdRP) confers resistance to favipiravir in vitro and in cell culture. This mutation has a cost to viral fitness, but fitness can be restored by a P653L mutation in the PA subunit of the polymerase. K229R also conferred favipiravir resistance to RNA polymerases of other influenza A virus strains, and its location within a highly conserved structural feature of the RdRP suggests that other RNA viruses might also acquire resistance through mutations in motif F. The mutations identified here could be used to screen influenza virus-infected patients treated with favipiravir for the emergence of resistance.


2009 ◽  
Vol 54 (13) ◽  
pp. 2179-2192 ◽  
Author(s):  
Bin Wu ◽  
ChengMin Wang ◽  
GuoYing Dong ◽  
Jing Luo ◽  
BaoHua Zhao ◽  
...  

2014 ◽  
Vol 281 (1787) ◽  
pp. 20133051 ◽  
Author(s):  
Andreas Handel ◽  
Camille Lebarbenchon ◽  
David Stallknecht ◽  
Pejman Rohani

Trade-offs between different components of a pathogen's replication and transmission cycle are thought to be common. A number of studies have identified trade-offs that emerge across scales, reflecting the tension between strategies that optimize within-host proliferation and large-scale population spread. Most of these studies are theoretical in nature, with direct experimental tests of such cross-scale trade-offs still rare. Here, we report an analysis of avian influenza A viruses across scales, focusing on the phenotype of temperature-dependent viral persistence. Taking advantage of a unique dataset that reports both environmental virus decay rates and strain-specific viral kinetics from duck challenge experiments, we show that the temperature-dependent environmental decay rate of a strain does not impact within-host virus load. Hence, for this phenotype, the scales of within-host infection dynamics and between-host environmental persistence do not seem to interact: viral fitness may be optimized on each scale without cross-scale trade-offs. Instead, we confirm the existence of a temperature-dependent persistence trade-off on a single scale, with some strains favouring environmental persistence in water at low temperatures while others reduce sensitivity to increasing temperatures. We show that this temperature-dependent trade-off is a robust phenomenon and does not depend on the details of data analysis. Our findings suggest that viruses might employ different environmental persistence strategies, which facilitates the coexistence of diverse strains in ecological niches. We conclude that a better understanding of the transmission and evolutionary dynamics of influenza A viruses probably requires empirical information regarding both within-host dynamics and environmental traits, integrated within a combined ecological and within-host framework.


2018 ◽  
Vol 111 ◽  
pp. 443-449 ◽  
Author(s):  
Camilly P. Pires de Mello ◽  
George L. Drusano ◽  
Jonathan R. Adams ◽  
Matthew Shudt ◽  
Robert Kulawy ◽  
...  

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