scholarly journals A9 Deep sequencing analysis to investigate the importance of within host genetic diversity and evolution of influenza A viruses for the development of resistance against neuraminidase inhibitors

2017 ◽  
Vol 3 (suppl_1) ◽  
Author(s):  
R. Roosenhoff ◽  
A. van der Linden ◽  
M. Schutten ◽  
R.A.M. Fouchier
Keyword(s):  
Genetic Diversity ◽  
Deep Sequencing ◽  
Influenza A ◽  
Sequencing Analysis ◽  
Neuraminidase Inhibitors ◽  
Influenza A Viruses ◽  
Development Of Resistance ◽  
Host Genetic ◽  
Deep Sequencing Analysis

scholarly journals Correction: Impact of Pregnancy on Intra-Host Genetic Diversity of Influenza A Viruses in Hospitalised Women: A Retrospective Cohort Study. J. Clin. Med. 2020, 9, 1974

2019 ◽  
Vol 9 (1) ◽  
pp. 58
Author(s):  
Gregory Destras ◽  
Maxime Pichon ◽  
Bruno Simon ◽  
Martine Valette ◽  
Vanessa Escuret ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Influenza A ◽  
Influenza A Viruses ◽  
Host Genetic

The authors wish to make the following corrections to this paper [...]

scholarly journals Evolution of Oseltamivir Resistance Mutations in Influenza A(H1N1) and A(H3N2) Viruses during Selection in Experimentally Infected Mice

2014 ◽  
Vol 58 (11) ◽  
pp. 6398-6405 ◽  
Author(s):  
Andrés Pizzorno ◽  
Yacine Abed ◽  
Pier-Luc Plante ◽  
Julie Carbonneau ◽  
Mariana Baz ◽  
...  
Keyword(s):  
Deep Sequencing ◽  
Influenza A ◽  
Influenza Viruses ◽  
H3n2 Virus ◽  
Sequencing Analysis ◽  
Resistance Mutations ◽  
Oseltamivir Resistance ◽  
Deep Sequencing Analysis ◽  
Selection Of

ABSTRACTThe evolution of oseltamivir resistance mutations during selection through serial passages in animals is still poorly described. Herein, we assessed the evolution of neuraminidase (NA) and hemagglutinin (HA) genes of influenza A/WSN/33 (H1N1) and A/Victoria/3/75 (H3N2) viruses recovered from the lungs of experimentally infected BALB/c mice receiving suboptimal doses (0.05 and 1 mg/kg of body weight/day) of oseltamivir over two generations. The traditional phenotypic and genotypic methods as well as deep-sequencing analysis were used to characterize the potential selection of mutations and population dynamics of oseltamivir-resistant variants. No oseltamivir-resistant NA or HA changes were detected in the recovered A/WSN/33 viruses. However, we observed a positive selection of the I222T NA substitution in the recovered A/Victoria/3/75 viruses, with a frequency increasing over time and with an oseltamivir concentration from 4% in the initial pretherapy inoculum up to 28% after two lung passages. Although the presence of mixed I222T viral populations in mouse lungs only led to a minimal increase in oseltamivir 50% enzyme-inhibitory concentrations (IC50s) (by a mean of 5.7-fold) compared to that of the baseline virus, the expressed recombinant A/Victoria/3/75 I222T NA protein displayed a 16-fold increase in the oseltamivir IC50level compared to that of the recombinant wild type (WT). In conclusion, the combination of serialin vivopassages under neuraminidase inhibitor (NAI) pressure and temporal deep-sequencing analysis enabled, for the first time, the identification and selection of the oseltamivir-resistant I222T NA mutation in an influenza H3N2 virus. Additionalin vivoselection experiments with other antivirals and drug combinations might provide important information on the evolution of antiviral resistance in influenza viruses.

scholarly journals Deep Sequencing Reveals Potential Antigenic Variants at Low Frequencies in Influenza A Virus-Infected Humans

2016 ◽  
Vol 90 (7) ◽  
pp. 3355-3365 ◽  
Author(s):  
Jorge M. Dinis ◽  
Nicholas W. Florek ◽  
Omolayo O. Fatola ◽  
Louise H. Moncla ◽  
James P. Mutschler ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Influenza Virus ◽  
Deep Sequencing ◽  
Influenza A ◽  
Rapid Evolution ◽  
Low Frequency ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Host Genetic ◽  
Antigenic Evolution

ABSTRACTInfluenza vaccines must be frequently reformulated to account for antigenic changes in the viral envelope protein, hemagglutinin (HA). The rapid evolution of influenza virus under immune pressure is likely enhanced by the virus's genetic diversity within a host, although antigenic change has rarely been investigated on the level of individual infected humans. We used deep sequencing to characterize the between- and within-host genetic diversity of influenza viruses in a cohort of patients that included individuals who were vaccinated and then infected in the same season. We characterized influenza HA segments from the predominant circulating influenza A subtypes during the 2012-2013 (H3N2) and 2013-2014 (pandemic H1N1; H1N1pdm) flu seasons. We found that HA consensus sequences were similar in nonvaccinated and vaccinated subjects. In both groups, purifying selection was the dominant force shaping HA genetic diversity. Interestingly, viruses from multiple individuals harbored low-frequency mutations encoding amino acid substitutions in HA antigenic sites at or near the receptor-binding domain. These mutations included two substitutions in H1N1pdm viruses, G158K and N159K, which were recently found to confer escape from virus-specific antibodies. These findings raise the possibility that influenza antigenic diversity can be generated within individual human hosts but may not become fixed in the viral population even when they would be expected to have a strong fitness advantage. Understanding constraints on influenza antigenic evolution within individual hosts may elucidate potential future pathways of antigenic evolution at the population level.IMPORTANCEInfluenza vaccines must be frequently reformulated due to the virus's rapid evolution rate. We know that influenza viruses exist within each infected host as a “swarm” of genetically distinct viruses, but the role of this within-host diversity in the antigenic evolution of influenza has been unclear. We characterized here the genetic and potential antigenic diversity of influenza viruses infecting humans, some of whom became infected despite recent vaccination. Influenza virus between- and within-host genetic diversity was not significantly different in nonvaccinated and vaccinated humans, suggesting that vaccine-induced immunity does not exert strong selective pressure on viruses replicating in individual people. We found low-frequency mutations, below the detection threshold of traditional surveillance methods, in nonvaccinated and vaccinated humans that were recently associated with antibody escape. Interestingly, these potential antigenic variants did not reach fixation in infected people, suggesting that other evolutionary factors may be hindering their emergence in individual humans.

Accumulation of segment 6 sgRNAs of influenza A viruses in the presence of neuraminidase inhibitors

2001 ◽  
Vol 1219 ◽  
pp. 845-853 ◽  
Author(s):  
Marina S Nedyalkova ◽  
Frederick G Hayden ◽  
Robert G Webster ◽  
Larisa V Gubareva
Keyword(s):  
Influenza A ◽  
Neuraminidase Inhibitors ◽  
Influenza A Viruses

scholarly journals Identification of non-invasive miRNAs biomarkers for prostate cancer by deep sequencing analysis of urinary exosomes

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Marta Rodríguez ◽  
Cristina Bajo-Santos ◽  
Nina P. Hessvik ◽  
Susanne Lorenz ◽  
Bastian Fromm ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Deep Sequencing ◽  
Sequencing Analysis ◽  
Non Invasive ◽  
Urinary Exosomes ◽  
Deep Sequencing Analysis

scholarly journals Novel insight into the non-coding repertoire through deep sequencing analysis

2012 ◽  
Vol 40 (11) ◽  
pp. e86-e86 ◽  
Author(s):  
Ofer Isakov ◽  
Roy Ronen ◽  
Judit Kovarsky ◽  
Aviram Gabay ◽  
Ido Gan ◽  
...  
Keyword(s):  
Deep Sequencing ◽  
Sequencing Analysis ◽  
Deep Sequencing Analysis ◽  
Insight Into

scholarly journals Characterization of Subtype H6 Avian Influenza A Viruses Isolated From Wild Birds in Poyang Lake, China

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhimin Wan ◽  
Qiuqi Kan ◽  
Zhehong Zhao ◽  
Hongxia Shao ◽  
Thomas J. Deliberto ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Avian Influenza ◽  
Mammalian Cells ◽  
Influenza A ◽  
Poyang Lake ◽  
Wild Birds ◽  
Mouse Lung ◽  
Influenza A Viruses ◽  
Domestic Poultry ◽  
History Of

Subtype H6 avian influenza A viruses (IAVs) are enzootic and genetically diverse in both domestic poultry and wild waterfowl and may cause spillovers in both pigs and humans. Thus, it is important to understand the genetic diversity of H6 IAVs in birds and their zoonotic potential. Compared with that in domestic poultry, the genetic diversity of H6 viruses in wild birds in China has not been well-understood. In this study, five H6 viruses were isolated from wild birds in Poyang Lake, China, and genetic analyses showed that these isolates are clustered into four genotypes associated with reassortments among avian IAVs from domestic poultry and wild birds in China and those from Eurasia and North America and that these viruses exhibited distinct phenotypes in growth kinetics analyses with avian and mammalian cells lines and in mouse challenge experiments. Of interest is that two H6 isolates from the Eurasian teal replicated effectively in the mouse lung without prior adaptation, whereas the other three did not. Our study suggested that there are variations in the mammalian viral replication efficiency phenotypic among genetically diverse H6 IAVs in wild birds and that both intra- and inter-continental movements of IAVs through wild bird migration may facilitate the emergence of novel H6 IAV reassortants with the potential for replicating in mammals, including humans. Continued surveillance to monitor the diversity of H6 IAVs in wild birds is necessary to increase our understanding of the natural history of IAVs.

scholarly journals Deep sequencing analysis of viral infection and evolution allows rapid and detailed characterization of viral mutant spectrum

2015 ◽  
Vol 31 (13) ◽  
pp. 2141-2150 ◽  
Author(s):  
Ofer Isakov ◽  
Antonio V. Bordería ◽  
David Golan ◽  
Amir Hamenahem ◽  
Gershon Celniker ◽  
...  
Keyword(s):  
Viral Infection ◽  
Deep Sequencing ◽  
Sequencing Analysis ◽  
Detailed Characterization ◽  
Viral Mutant ◽  
Mutant Spectrum ◽  
Deep Sequencing Analysis
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