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 Real-time characterization of the molecular epidemiology of an influenza pandemic

2013 ◽  
Vol 9 (5) ◽  
pp. 20130331 ◽  
Author(s):  
J. Hedge ◽  
S. J. Lycett ◽  
A. Rambaut
Keyword(s):  
Real Time ◽  
Influenza A ◽  
Sequence Data ◽  
Influenza Pandemic ◽  
H1n1 Influenza ◽  
Accurate Estimation ◽  
Time Estimates ◽  
Dataset Size ◽  
2009 H1n1

Early characterization of the epidemiology and evolution of a pandemic is essential for determining the most appropriate interventions. During the 2009 H1N1 influenza A pandemic, public databases facilitated widespread sharing of genetic sequence data from the outset. We use Bayesian phylogenetics to simulate real-time estimates of the evolutionary rate, date of emergence and intrinsic growth rate ( r 0 ) of the pandemic from whole-genome sequences. We investigate the effects of temporal range of sampling and dataset size on the precision and accuracy of parameter estimation. Parameters can be accurately estimated as early as two months after the first reported case, from 100 genomes and the choice of growth model is important for accurate estimation of r 0 . This demonstrates the utility of simple coalescent models to rapidly inform intervention strategies during a pandemic.

scholarly journals Pathogenic analysis of the pandemic 2009 H1N1 influenza A viruses in ferrets

2017 ◽  
Vol 79 (8) ◽  
pp. 1453-1460 ◽  
Author(s):  
Yoshimi TSUDA ◽  
Carla WEISEND ◽  
Cynthia MARTELLARO ◽  
Friederike FELDMANN ◽  
Elaine HADDOCK
Keyword(s):  
Influenza A ◽  
H1n1 Influenza ◽  
Influenza A Viruses ◽  
2009 H1n1 ◽  
Pathogenic Analysis

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 Inefficient Control of Host Gene Expression by the 2009 Pandemic H1N1 Influenza A Virus NS1 Protein

2010 ◽  
Vol 84 (14) ◽  
pp. 6909-6922 ◽  
Author(s):  
Benjamin G. Hale ◽  
John Steel ◽  
Rafael A. Medina ◽  
Balaji Manicassamy ◽  
Jianqiang Ye ◽  
...  
Keyword(s):  
Gene Expression ◽  
Influenza A Virus ◽  
Influenza A ◽  
H1n1 Virus ◽  
H1n1 Influenza ◽  
Ns1 Protein ◽  
Host Gene Expression ◽  
Wild Type ◽  
Influenza A Viruses ◽  
2009 H1n1

ABSTRACT In 2009, a novel swine-origin H1N1 influenza A virus emerged. Here, we characterize the multifunctional NS1 protein of this human pandemic virus in order to understand factors that may contribute to replication efficiency or pathogenicity. Although the 2009 H1N1 virus NS1 protein (2009/NS1) is an effective interferon antagonist, we found that this NS1 (unlike those of previous human-adapted influenza A viruses) is unable to block general host gene expression in human or swine cells. This property could be restored in 2009/NS1 by replacing R108, E125, and G189 with residues corresponding to human virus consensus. Mechanistically, these previously undescribed mutations acted by increasing binding of 2009/NS1 to the cellular pre-mRNA processing protein CPSF30. A recombinant 2009 H1N1 influenza A virus (A/California/04/09) expressing NS1 with these gain-of-function substitutions was more efficient than the wild type at antagonizing host innate immune responses in primary human epithelial cells. However, such mutations had no significant effect on virus replication in either human or swine tissue culture substrates. Surprisingly, in a mouse model of pathogenicity, the mutant virus appeared to cause less morbidity, and was cleared faster, than the wild type. The mutant virus also demonstrated reduced titers in the upper respiratory tracts of ferrets; however, contact and aerosol transmissibility of the virus was unaffected. Our data highlight a potential human adaptation of NS1 that seems absent in “classically derived” swine-origin influenza A viruses, including the 2009 H1N1 virus. We discuss the impact that a natural future gain of this NS1 function may have on the new pandemic virus in humans.

Pandemic influenza A (H1N1) virus infection and avian influenza A (H5N1) virus infection: a comparative analysisThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (4) ◽  
pp. 575-587 ◽  
Author(s):  
Christine Korteweg ◽  
Jiang Gu
Keyword(s):  
Virus Infection ◽  
Influenza A ◽  
Peer Review Process ◽  
Influenza Pandemic ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
H5n1 Influenza ◽  
Influenza A H1n1 ◽  
2009 H1n1

The 2009 H1N1 and H5N1 influenza viruses are newly (re-) emerged influenza A viruses (2009 A(H1N1) and A(H5N1), respectively) that have recently posed tremendous health threats in many regions worldwide. With the 2009 outbreak of H1N1 influenza A, the world witnessed the first influenza pandemic of the 21st century. The disease has rapidly spread across the entire globe, and has resulted in hundreds of thousands of cases with confirmed infection. Although characterized by high transmissibility, the virulence and fatality of the 2009 A(H1N1) influenza virus have thus far remained relatively low. The reverse holds true for A(H5N1) influenza; at a fatality rate that exceeds 60%, it is known to cause severe damage to the human respiratory system, but is not presently capable of efficient transmission from human to human. Apart from the clear differences between the two types of influenza, there are some significant similarities that warrant attention. In particular, the more severe and fatal 2009 A(H1N1) influenza cases have shown symptoms similar to those reported in cases of A(H5N1) influenza. Histopathological findings for these cases, to the extent available, also appear to have similarities for both diseases in terms of damage and severity. Here we review important recent publications in this area, and we discuss some of the key commonalities and contrasts between the two influenza A types in terms of their biology, origins, clinical features, pathology and pathogenesis, and receptors and transmissibility.

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.

scholarly journals Pandemic 2009 H1N1 Influenza A Virus Carrying a Q136K Mutation in the Neuraminidase Gene Is Resistant to Zanamivir but Exhibits Reduced Fitness in the Guinea Pig Transmission Model

2012 ◽  
Vol 87 (3) ◽  
pp. 1912-1915 ◽  
Author(s):  
Michael M. Kaminski ◽  
Annette Ohnemus ◽  
Peter Staeheli ◽  
Dennis Rubbenstroth
Keyword(s):  
Guinea Pig ◽  
Influenza A ◽  
H1n1 Influenza ◽  
Viral Fitness ◽  
Transmission Model ◽  
Influenza A Viruses ◽  
Viral Particles ◽  
2009 H1n1 ◽  
High Degree ◽  
Na Gene

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.

TMPRSS2 is essential for pathogenicity of H7N9 and H1N1 influenza A viruses in mice

Pneumologie ◽  
2014 ◽  
Vol 68 (02) ◽  
Author(s):  
C Tarnow ◽  
G Engels ◽  
A Arendt ◽  
F Schwalm ◽  
H Sediri ◽  
...  
Keyword(s):  
Influenza A ◽  
H1n1 Influenza ◽  
Influenza A Viruses
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