scholarly journals Comparison of Avian and Human Influenza A Viruses Reveals a Mutational Bias on the Viral Genomes

2006 ◽  
Vol 80 (23) ◽  
pp. 11887-11891 ◽  
Author(s):  
Raul Rabadan ◽  
Arnold J. Levine ◽  
Harlan Robins
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Genomic Sequence ◽  
Sequence Data ◽  
H1n1 Influenza ◽  
Mutational Bias ◽  
Influenza A Viruses ◽  
Viral Genomes ◽  
Avian Influenza Virus H5n1 ◽  
History Of

ABSTRACT In the last few years, the genomic sequence data for thousands of influenza A virus strains, including the 1918 pandemic strain, and hundreds of isolates of the avian influenza virus H5N1, which is causing an increasing number of human fatalities, have become publicly available. This large quantity of sequence data allows us to do comparative genomics with the human and avian versions of the virus. We find that the nucleotide compositions of influenza A viruses infecting the two hosts are sufficiently different that we can determine the host at almost 100% accuracy. This assignment works at the segment level, which allows us to construct the reassortment history of individual segments within each strain. We suggest that the different nucleotide compositions can be explained by a host-dependent mutation bias. To support this idea, we estimate the fixation rates for the different polymerase segments and the ratios of synonymous to nonsynonymous changes. Additionally, we provide evidence supporting the hypothesis that the H1N1 influenza virus entered the human population just prior to the 1918 outbreak, with an earliest bound of 1910.

scholarly journals Spatiotemporal Distribution and Evolution of the A/H1N1 2009 Pandemic Influenza Virus in Pigs in France from 2009 to 2017: Identification of a Potential Swine-Specific Lineage

2018 ◽  
Vol 92 (24) ◽  
Author(s):  
Amélie Chastagner ◽  
Séverine Hervé ◽  
Emilie Bonin ◽  
Stéphane Quéguiner ◽  
Edouard Hirchaud ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Phylogenetic Analyses ◽  
Swine Influenza ◽  
H1n1 Influenza ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Evolutionary Patterns ◽  
Increased Risk ◽  
Na Sequences

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.

scholarly journals Importin-α7 Is Required for Enhanced Influenza A Virus Replication in the Alveolar Epithelium and Severe Lung Damage in Mice

2014 ◽  
Vol 88 (14) ◽  
pp. 8166-8179 ◽  
Author(s):  
Patricia Resa-Infante ◽  
René Thieme ◽  
Thomas Ernst ◽  
Petra C. Arck ◽  
Harald Ittrich ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Replication ◽  
Influenza A ◽  
Ex Vivo ◽  
Alveolar Epithelium ◽  
Severe Pneumonia ◽  
H1n1 Influenza ◽  
Lung Damage ◽  
Influenza A Viruses ◽  
Mononuclear Infiltration

ABSTRACTInfluenza A viruses recruit components of the nuclear import pathway to enter the host cell nucleus and promote viral replication. Here, we analyzed the role of the nuclear import factor importin-α7 in H1N1 influenza virus pulmonary tropism by using variousex vivoimaging techniques (magnetic resonance imaging, confocal laser scanning microscopy, and correlative light-electron microscopy). We infected importin-α7 gene-deficient (α7−/−) mice with a recombinant H1N1 influenza virus and compared thein vivoviral kinetics with those in wild-type (WT) mice. In WT mice, influenza virus replication in the bronchial and alveolar epithelium already occurred a few days after infection. Accordingly, extensive mononuclear infiltration and alveolar destruction were present in the lungs of infected WT mice, followed by 100% lethality. Conversely, in α7−/−mice, virus replication was restricted mostly to the bronchial epithelium with marginal alveolar infection, resulting in significantly reduced lung damage and enhanced animal survival. To investigate the host immune response during alveolar virus replication, we studied the role of primary macrophages in virus propagation and clearance. The ability of macrophages to support or clear the virus infection, as well as the host cellular immune responses, did not significantly differ between WT and α7−/−mice. However, cytokine and chemokine responses were generally elevated in WT mice, likely reflective of increased viral replication in the lung. In summary, these data show that a cellular factor, importin-α7, is required for enhanced virus replication in the alveolar epithelium, resulting in elevated cytokine and chemokine levels, extensive mononuclear infiltration, and thus, severe pneumonia and enhanced virulence in mice.IMPORTANCEInfluenza A viruses are respiratory pathogens that may cause pneumonia in humans. Viral infection and replication in the alveoli of the respiratory tract are believed to be crucial for the development of the acute respiratory distress syndrome associated with fatal outcomes in influenza virus-infected patients. Here, we report the requirement of a cellular factor, importin-α7, for efficient virus replication in the alveolar epithelium of mice. Using complementaryex vivoimaging approaches, we show that influenza virus replication is restricted to the bronchial epithelium, followed by enhanced survival in importin-α7-deficient mice. In contrast, the presence of this gene results in enhanced virus replication in the alveoli, elevated cytokine and chemokine responses, mononuclear infiltration, alveolar destruction, and 100% lethality in wild-type mice. Taken together, our results show that importin-α7 is particularly required for virus replication in the alveolar epithelium in association with severe pneumonia and death in mice.

scholarly journals Stochastic processes dominate the within and between host evolution of influenza virus

2017 ◽  
Author(s):  
John T. McCrone ◽  
Robert J. Woods ◽  
Emily T. Martin ◽  
Ryan E. Malosh ◽  
Arnold S. Monto ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Stochastic Processes ◽  
Influenza A ◽  
Evolutionary Dynamics ◽  
Sequence Data ◽  
Influenza A Viruses ◽  
Effective Population ◽  
The Individual ◽  
Host Evolution

AbstractThe global evolutionary dynamics of influenza virus ultimately derive from processes that take place within and between infected individuals. Here we define the dynamics of influenza A virus populations in human hosts through next generation sequencing of 249 specimens from 200 individuals collected over 6290 person-seasons of observation. Because these viruses were collected over 5 seasons from individuals in a prospective community-based cohort, they are broadly representative of natural human infections with seasonal viruses. We used viral sequence data from 35 serially sampled individuals to estimate a within host effective population size of 30-70 and an in vivo mutation rate of 4x10−5 per nucleotide per cellular infectious cycle. These estimates are consistent across several models and robust to the models' underlying assumptions. We also identified 43 epidemiologically linked and genetically validated transmission pairs. Maximum likelihood optimization of multiple transmission models estimates an effective transmission bottleneck of 1-2 distinct genomes. Our data suggest that positive selection of novel viral variants is inefficient at the level of the individual host and that genetic drift and other stochastic processes dominate the within and between host evolution of influenza A viruses.

scholarly journals Phylogeographic reconstruction using air transportation data and its application to the 2009 H1N1 influenza A pandemic

2019 ◽  
Author(s):  
Susanne Reimering ◽  
Sebastian Muñoz ◽  
Alice C. McHardy
Keyword(s):  
Influenza A ◽  
State Of The Art ◽  
Sequence Data ◽  
Air Transportation ◽  
H1n1 Influenza ◽  
Real Sequence ◽  
Influenza A Viruses ◽  
Geographic Spread ◽  
2009 H1n1 ◽  
Genetic Sequences

AbstractInfluenza A viruses cause seasonal epidemics and occasional pandemics in the human population. While the worldwide circulation of seasonal influenza is at least partly understood, the exact migration patterns between countries, states or cities are not well studied. Here, we use the Sankoff algorithm for parsimonious phylogeographic reconstruction together with effective distances based on a worldwide air transportation network. By first simulating geographic spread and then phylogenetic trees and genetic sequences, we confirmed that reconstructions with effective distances inferred phylogeographic spread more accurately than reconstructions with geographic distances and Bayesian reconstructions with BEAST, the current state-of-the-art. Our method extends the state-of-the-art by using fine-grained locations like airports and inferring intermediate locations not observed among sampled isolates. When applied to sequence data of the pandemic H1N1 influenza A virus in 2009, our approach correctly inferred the origin and proposed airports mainly involved in the spread of the virus. In case of a novel outbreak, this approach allows to rapidly analyze sequence data and infer origin and spread routes to improve disease surveillance and control.Author summaryInfluenza A viruses infect up to 5 million people in recurring epidemics every year. Further, viruses of zoonotic origin constantly pose a pandemic risk. Understanding the geographical spread of these viruses, including the origin and the main spread routes between cities, states or countries, could help to monitor or contain novel outbreaks. Based on genetic sequences and sampling locations, the geographic spread can be reconstructed along a phylogenetic tree. Our approach uses a parsimonious reconstruction with air transportation data and was verified using a simulation of the 2009 H1N1 influenza A pandemic. Applied to real sequence data of the outbreak, our analysis gave detailed insights into spread patterns of influenza A viruses, highlighting the origin as well as airports mainly involved in the spread.

scholarly journals Could Environment Affect the Mutation of H1N1 Influenza Virus?

2020 ◽  
Vol 17 (9) ◽  
pp. 3092
Author(s):  
Dong Jiang ◽  
Qian Wang ◽  
Zhihua Bai ◽  
Heyuan Qi ◽  
Juncai Ma ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Environmental Factors ◽  
Social Development ◽  
Influenza A ◽  
H1n1 Influenza ◽  
Influenza A Viruses ◽  
Nighttime Light ◽  
Complex Relationships ◽  
The Impact ◽  
The Relationship

H1N1 subtype influenza A viruses are the most common type of influenza A virus to infect humans. The two major outbreaks of the virus in 1918 and 2009 had a great impact both on human health and social development. Though data on their complete genome sequences have recently been obtained, the evolution and mutation of A/H1N1 viruses remain unknown to this day. Among many drivers, the impact of environmental factors on mutation is a novel hypothesis worth studying. Here, a geographically disaggregated method was used to explore the relationship between environmental factors and mutation of A/H1N1 viruses from 2000–2019. All of the 11,721 geo-located cases were examined and the data was analysed of six environmental elements according to the time and location (latitude and longitude) of those cases. The main mutation value was obtained by comparing the sequence of the influenza virus strain with the earliest reported sequence. It was found that environmental factors systematically affect the mutation of A/H1N1 viruses. Minimum temperature displayed a nonlinear, rising association with mutation, with a maximum ~15 °C. The effects of precipitation and social development index (nighttime light) were more complex, while population density was linearly and positively correlated with mutation of A/H1N1 viruses. Our results provide novel insight into understanding the complex relationships between mutation of A/H1N1 viruses and environmental factors.

scholarly journals A non-neutralizing antibody broadly protects against influenza virus infection by engaging effector cells

2021 ◽  
Vol 17 (8) ◽  
pp. e1009724
Author(s):  
Yi-An Ko ◽  
Yueh-Hsiang Yu ◽  
Yen-Fei Wu ◽  
Yung-Chieh Tseng ◽  
Chia-Lin Chen ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Protective Efficacy ◽  
Lethal Dose ◽  
Influenza Virus Infection ◽  
Neutralizing Antibody ◽  
H1n1 Influenza ◽  
Influenza A Viruses

Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HAmg) produced cross-strain-reactive antibodies and were better protected than mice injected with a fully glycosylated HA (HAfg) during lethal dose challenge. We employed a single B-cell screening platform to isolate the cross-protective monoclonal antibody (mAb) 651 from mice immunized with the HAmg of A/Brisbane/59/2007 (H1N1) influenza virus (Bris/07). The mAb 651 recognized the head domain of a broad spectrum of HAs from groups 1 and 2 influenza A viruses and offered prophylactic and therapeutic efficacy against A/California/07/2009 (H1N1) (Cal/09) and Bris/07 infections in mice. The antibody did not possess neutralizing activity; however, antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis mediated by natural killer cells and alveolar macrophages were important in the protective efficacy of mAb 651. Together, this study highlighted the significance of effector functions for non-neutralizing antibodies to exhibit protection against influenza virus infection.

scholarly journals Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission

2020 ◽  
Author(s):  
Yifei Xu ◽  
Kuiama Lewandowski ◽  
Louise O Downs ◽  
James Kavanagh ◽  
Thomas Hender ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Influenza Virus ◽  
Influenza A ◽  
Sequence Data ◽  
Diagnostic Testing ◽  
Nosocomial Transmission ◽  
Molecular Diagnostic ◽  
Metagenomic Sequencing ◽  
Influenza A Viruses ◽  
Genome Phylogeny

ABSTRACTBackgroundInfluenza virus presents a significant challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid diagnosis of infection, rationalising antimicrobial therapy, and supporting interventions for infection control. This study aimed to evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings.MethodsWe conducted Nanopore metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic testing. We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data.ResultsMetagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses compared with the diagnostic standard (Cepheid Xpress/BioFire FilmArray Respiratory Panel). We identified a H3N2 genome with the oseltamivir resistant S331R mutation in the NA protein, potentially associated with the emergence of a distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in the infectious diseases ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant strain circulating in the community. We also detected a range of other potentially pathogenic viruses and bacteria from the metagenome.ConclusionNanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Generation of full genomes can contribute to the investigation and management of nosocomial outbreaks.

scholarly journals Sweep Dynamics (SD) plots: Computational identification of selective sweeps to monitor the adaptation of influenza A viruses

2017 ◽  
Author(s):  
Thorsten R. Klingen ◽  
Susanne Reimering ◽  
Jens Loers ◽  
Kyra Mooren ◽  
Frank Klawonn ◽  
...  
Keyword(s):  
Influenza A ◽  
Sequence Data ◽  
Rapid Evolution ◽  
Selective Advantage ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Computational Method ◽  
Selective Sweeps ◽  
Influenza A Viruses ◽  
Novel Host

AbstractMonitoring changes in influenza A virus genomes is crucial to understand its rapid evolution and adaptation to changing conditions e.g. establishment within novel host species. Selective sweeps represent a rapid mode of adaptation and are typically observed in human influenza A viruses. We describe Sweep Dynamics (SD) plots, a computational method combining phylogenetic algorithms with statistical techniques to characterize the molecular adaptation of rapidly evolving viruses from longitudinal sequence data. To our knowledge, it is the first method that identifies selective sweeps, the time periods in which these occurred and associated changes providing a selective advantage to the virus. We studied the past genome-wide adaptation of the 2009 pandemic H1N1 influenza A (pH1N1) and seasonal H3N2 influenza A (sH3N2) viruses. The pH1N1 influenza virus showed simultaneous amino acid changes in various proteins, particularly in seasons of high pH1N1 activity. Partially, these changes resulted in functional alterations facilitating sustained human-to-human transmission. In the evolution of sH3N2 influenza viruses, we detected changes characterizing vaccine strains, which were occasionally revealed in selective sweeps one season prior to the WHO recommendation. Taken together, SD plots allow monitoring and characterizing the adaptive evolution of influenza A viruses by identifying selective sweeps and their associated signatures.

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