scholarly journals TreeKnit: Inferring Ancestral Reassortment Graphs of influenza viruses

2021 ◽  
Author(s):  
Pierre Barrat-Charlaix ◽  
Timothy Vaughan ◽  
Richard Neher
Keyword(s):  
Genetic Diversity ◽  
Pandemic Influenza ◽  
Bayesian Method ◽  
Seasonal Influenza ◽  
Sequence Data ◽  
Influenza Viruses ◽  
Viral Sequence ◽  
Wide Range

When two influenza viruses co-infect the same cell, they can exchange genome segments in a process known as reassortment. Reassortment is an important source of genetic diversity and is known to have been involved in the emergence of most pandemic influenza strains. However, because of the difficulty in identifying reassortments events from viral sequence data, little is known about its role in the evolution of the seasonal influenza viruses. Here we introduce TreeKnit, a method that infers ancestral reassortment graphs (ARG) from two segment trees. It is based on topological differences between trees, and proceeds in a greedy fashion by finding regions that are compatible in the two trees. Using simulated genealogies with reassortments, we show that TreeKnit performs well in a wide range of settings and that it is as accurate as a more principled bayesian method, while being orders of magnitude faster. Finally, we show that it is possible to use the inferred ARG to better resolve segment trees and to construct more informative visualizations of reassortments.

scholarly journals Improving pandemic influenza risk assessment

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Colin A Russell ◽  
Peter M Kasson ◽  
Ruben O Donis ◽  
Steven Riley ◽  
John Dunbar ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Sequence Data ◽  
Virus Genome ◽  
Influenza Viruses ◽  
Influenza Surveillance ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Virus Genotype

Assessing the pandemic risk posed by specific non-human influenza A viruses is an important goal in public health research. As influenza virus genome sequencing becomes cheaper, faster, and more readily available, the ability to predict pandemic potential from sequence data could transform pandemic influenza risk assessment capabilities. However, the complexities of the relationships between virus genotype and phenotype make such predictions extremely difficult. The integration of experimental work, computational tool development, and analysis of evolutionary pathways, together with refinements to influenza surveillance, has the potential to transform our ability to assess the risks posed to humans by non-human influenza viruses and lead to improved pandemic preparedness and response.

scholarly journals Prediction, dynamics, and visualization of antigenic phenotypes of seasonal influenza viruses

2016 ◽  
Vol 113 (12) ◽  
pp. E1701-E1709 ◽  
Author(s):  
Richard A. Neher ◽  
Trevor Bedford ◽  
Rodney S. Daniels ◽  
Colin A. Russell ◽  
Boris I. Shraiman
Keyword(s):  
Influenza Virus ◽  
Seasonal Influenza ◽  
Sequence Data ◽  
Influenza Viruses ◽  
Surface Glycoprotein ◽  
Amino Acid Substitutions ◽  
Model Output ◽  
Virus Population ◽  
Web Browser ◽  
Antigenic Properties

Human seasonal influenza viruses evolve rapidly, enabling the virus population to evade immunity and reinfect previously infected individuals. Antigenic properties are largely determined by the surface glycoprotein hemagglutinin (HA), and amino acid substitutions at exposed epitope sites in HA mediate loss of recognition by antibodies. Here, we show that antigenic differences measured through serological assay data are well described by a sum of antigenic changes along the path connecting viruses in a phylogenetic tree. This mapping onto the tree allows prediction of antigenicity from HA sequence data alone. The mapping can further be used to make predictions about the makeup of the future A(H3N2) seasonal influenza virus population, and we compare predictions between models with serological and sequence data. To make timely model output readily available, we developed a web browser-based application that visualizes antigenic data on a continuously updated phylogeny.

scholarly journals In Vitro Antiviral Activity of Favipiravir (T-705) against Drug-Resistant Influenza and 2009 A(H1N1) Viruses

2010 ◽  
Vol 54 (6) ◽  
pp. 2517-2524 ◽  
Author(s):  
Katrina Sleeman ◽  
Vasiliy P. Mishin ◽  
Varough M. Deyde ◽  
Yousuke Furuta ◽  
Alexander I. Klimov ◽  
...  
Keyword(s):  
Influenza A ◽  
Seasonal Influenza ◽  
Mdck Cells ◽  
Antiviral Effect ◽  
Plaque Formation ◽  
Influenza Viruses ◽  
New Drugs ◽  
Yield Reduction ◽  
Wide Range

ABSTRACT Favipiravir (T-705) has previously been shown to have a potent antiviral effect against influenza virus and some other RNA viruses in both cell culture and in animal models. Currently, favipiravir is undergoing clinical evaluation for the treatment of influenza A and B virus infections. In this study, favipiravir was evaluated in vitro for its ability to inhibit the replication of a representative panel of seasonal influenza viruses, the 2009 A(H1N1) strains, and animal viruses with pandemic (pdm) potential (swine triple reassortants, H2N2, H4N2, avian H7N2, and avian H5N1), including viruses which are resistant to the currently licensed anti-influenza drugs. All viruses were tested in a plaque reduction assay with MDCK cells, and a subset was also tested in both yield reduction and focus inhibition (FI) assays. For the majority of viruses tested, favipiravir significantly inhibited plaque formation at 3.2 μM (0.5 μg/ml) (50% effective concentrations [EC50s] of 0.19 to 22.48 μM and 0.03 to 3.53 μg/ml), and for all viruses, with the exception of a single dually resistant 2009 A(H1N1) virus, complete inhibition of plaque formation was seen at 3.2 μM (0.5 μg/ml). Due to the 2009 pandemic and increased drug resistance in circulating seasonal influenza viruses, there is an urgent need for new drugs which target influenza. This study demonstrates that favipiravir inhibits in vitro replication of a wide range of influenza viruses, including those resistant to currently available drugs.

scholarly journals Bayesian inference of reassortment networks reveals fitness benefits of reassortment in human influenza viruses

2020 ◽  
Vol 117 (29) ◽  
pp. 17104-17111
Author(s):  
Nicola F. Müller ◽  
Ugnė Stolz ◽  
Gytis Dudas ◽  
Tanja Stadler ◽  
Timothy G. Vaughan
Keyword(s):  
Genetic Diversity ◽  
Phylogenetic Trees ◽  
Sequence Data ◽  
Population Level ◽  
Influenza Viruses ◽  
Monte Carlo Algorithm ◽  
Full Genome Sequence ◽  
Full Genome ◽  
Human Influenza ◽  
Fitness Benefits

Reassortment is an important source of genetic diversity in segmented viruses and is the main source of novel pathogenic influenza viruses. Despite this, studying the reassortment process has been constrained by the lack of a coherent, model-based inference framework. Here, we introduce a coalescent-based model that allows us to explicitly model the joint coalescent and reassortment process. In order to perform inference under this model, we present an efficient Markov chain Monte Carlo algorithm to sample rooted networks and the embedding of phylogenetic trees within networks. This algorithm provides the means to jointly infer coalescent and reassortment rates with the reassortment network and the embedding of segments in that network from full-genome sequence data. Studying reassortment patterns of different human influenza datasets, we find large differences in reassortment rates across different human influenza viruses. Additionally, we find that reassortment events predominantly occur on selectively fitter parts of reassortment networks showing that on a population level, reassortment positively contributes to the fitness of human influenza viruses.

scholarly journals Contemporary Seasonal Influenza A (H1N1) Virus Infection Primes for a More Robust Response To Split Inactivated Pandemic Influenza A (H1N1) Virus Vaccination in Ferrets

2010 ◽  
Vol 17 (12) ◽  
pp. 1998-2006 ◽  
Author(s):  
Ali H. Ellebedy ◽  
Thomas P. Fabrizio ◽  
Ghazi Kayali ◽  
Thomas H. Oguin ◽  
Scott A. Brown ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Seasonal Influenza ◽  
H1n1 Virus ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Inactivated Vaccine ◽  
H1n1 Influenza Virus ◽  
Influenza A H1n1

ABSTRACT Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8+ cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans.

scholarly journals Bayesian inference of reassortment networks reveals fitness benefits of reassortment in human influenza viruses

2019 ◽  
Author(s):  
Nicola F. Müller ◽  
Ugnė Stolz ◽  
Gytis Dudas ◽  
Tanja Stadler ◽  
Timothy G. Vaughan
Keyword(s):  
Genetic Diversity ◽  
Phylogenetic Trees ◽  
Sequence Data ◽  
Population Level ◽  
Influenza Viruses ◽  
Monte Carlo Algorithm ◽  
Full Genome Sequence ◽  
Full Genome ◽  
Human Influenza ◽  
Fitness Benefits

AbstractReassortment is an important source of genetic diversity in segmented viruses and is the main source of novel pathogenic influenza viruses. Despite this, studying the reassortment process has been constrained by the lack of a coherent, model-based inference framework. We here introduce a novel coalescent based model that allows us to explicitly model the joint coalescent and reassortment process. In order to perform inference under this model, we present an efficient Markov chain Monte Carlo algorithm to sample rooted networks and the embedding of phylogenetic trees within networks. Together, these provide the means to jointly infer coalescent and reassortment rates with the reassortment network and the embedding of segments in that network from full genome sequence data. Studying reassortment patterns of different human influenza datasets, we find large differences in reassortment rates across different human influenza viruses. Additionally, we find that reassortment events predominantly occur on selectively fitter parts of reassortment networks showing that on a population level, reassortment positively contributes to the fitness of human influenza viruses.

scholarly journals H1N1 INFLUENZA VERSUS SEASONAL INFLUENZA MORBIDITY AND MORTALITY: A PROSPECTIVE STUDY IN AL-KINDY TEACHING HOSPITAL/ IRAQ-BAGHDAD

2016 ◽  
Vol 12 (2) ◽  
pp. 18-21
Author(s):  
Ismail A. Hussain AL-Ameri ◽  
Baker Fadel ◽  
Ali Sajid ◽  
Imad Kareem
Keyword(s):  
Teaching Hospital ◽  
Seasonal Influenza ◽  
Influenza Pandemic ◽  
Age Groups ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Morbidity And Mortality ◽  
Severe Illness ◽  
Wide Range ◽  
Symptoms And Signs

Background: H1N1 influenza pandemic or swine flu was an influenza pandemic first described in Iraq in October 2009 .The virus appeared to be anew strain of H1N1 causes wide range of morbidity and mortality among different genders and age groups as part of worldwide pandemics.Seasonal flu is a contagious respiratory illness caused by influenza viruses that infect the nose, throat, and lungs. It can cause mild to severe illness, and at times can lead to death. The best way to prevent the flu is by getting a flu vaccine each year. Objectives: Is to determine the morbidity and mortality in different age groups in patients with H1N1 influenza versus those patients with seasonal influenza who were admitted at the same time to AL-kindy teaching hospital during pandemic 2009. Type of the study: A retrospective observational study. Methods: A total number of 210 cases with influenza symptoms and signs were included in this study which was conducted at AL-kindy teaching hospital , Baghdad, Iraq at inpatient medical wards over a period from October to December 2009. All cases were tested by real time PCR for H1N1 influenza virus by taking nasal and throat swab in addition to monitoring symptoms and signs of influenza and chest radiographs. Results: Out of 210 cases, 90 (42.85%) cases were positive for H1N1 influenza and 120 (57.14%) cases had negative test are considered having seasonal influenza. Of the positive cases(64.44%) were males and (35.55%) were females. Of negative cases(seasonal flu)male gender were (61.66%) , while female gender were (38.33%). 57.77% of positive cases developed flue like illness compared with 54.16% of negative while 25.55% of positive developed pneumonia compared with 22.5% of negative.5.55% of positive cases developed ARDS compared with 5% only in negative cases.11.11% had different presentation in positive cases (bronchitis ,gastroenteritis) while 18.33%of negative. Mortality in positive cases are 14.4% compared with only 10% in negative cases. Conclusions: Influenza A/H1N1had same symptoms and signs of epidemic seasonal influenza but run aggressive and short course of morbidity in 3-5 days with high percentage of complication and high mortality compared with seasonal epidemic influenza with rare affection above 65 years old, both groups had same incidence of complication with pneumonia and ARDS

scholarly journals Serum Samples From Middle-aged Adults Vaccinated Annually with Seasonal Influenza Vaccines Cross-neutralize Some Potential Pandemic Influenza Viruses

2015 ◽  
Vol 213 (3) ◽  
pp. 403-406 ◽  
Author(s):  
Wei Wang ◽  
Esmeralda Alvarado-Facundo ◽  
Qiong Chen ◽  
Christine M. Anderson ◽  
Dorothy Scott ◽  
...  
Keyword(s):  
Pandemic Influenza ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Middle Aged ◽  
Serum Samples ◽  
Middle Aged Adults

scholarly journals Characterising the epidemic spread of influenza A/H3N2 within a city through phylogenetics

2020 ◽  
Vol 16 (11) ◽  
pp. e1008984
Author(s):  
Nicola F. Müller ◽  
Daniel Wüthrich ◽  
Nina Goldman ◽  
Nadine Sailer ◽  
Claudia Saalfrank ◽  
...  
Keyword(s):  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Season ◽  
Sequence Data ◽  
The Elderly ◽  
Influenza Viruses ◽  
Transmission Network ◽  
School Closures ◽  
School Aged Children ◽  
Private Practitioners

Infecting large portions of the global population, seasonal influenza is a major burden on societies around the globe. While the global source sink dynamics of the different seasonal influenza viruses have been studied intensively, its local spread remains less clear. In order to improve our understanding of how influenza is transmitted on a city scale, we collected an extremely densely sampled set of influenza sequences alongside patient metadata. To do so, we sequenced influenza viruses isolated from patients of two different hospitals, as well as private practitioners in Basel, Switzerland during the 2016/2017 influenza season. The genetic sequences reveal that repeated introductions into the city drove the influenza season. We then reconstruct how the effective reproduction number changed over the course of the season. While we did not find that transmission dynamics in Basel correlate with humidity or school closures, we did find some evidence that it may positively correlated with temperature. Alongside the genetic sequence data that allows us to see how individual cases are connected, we gathered patient information, such as the age or household status. Zooming into the local transmission outbreaks suggests that the elderly were to a large extent infected within their own transmission network. In the remaining transmission network, our analyses suggest that school-aged children likely play a more central role than pre-school aged children. These patterns will be valuable to plan interventions combating the spread of respiratory diseases within cities given that similar patterns are observed for other influenza seasons and cities.

scholarly journals Global transmission of influenza viruses from humans to swine

2012 ◽  
Vol 93 (10) ◽  
pp. 2195-2203 ◽  
Author(s):  
Martha I. Nelson ◽  
Marie R. Gramer ◽  
Amy L. Vincent ◽  
Edward C. Holmes
Keyword(s):  
Genetic Diversity ◽  
Phylogenetic Analysis ◽  
Influenza Virus ◽  
Large Scale ◽  
Sequence Data ◽  
Virus Genome ◽  
Influenza Viruses ◽  
Substantial Contribution ◽  
Human Influenza ◽  
Swine Workers

To determine the extent to which influenza viruses jump between human and swine hosts, we undertook a large-scale phylogenetic analysis of pandemic A/H1N1/09 (H1N1pdm09) influenza virus genome sequence data. From this, we identified at least 49 human-to-swine transmission events that occurred globally during 2009–2011, thereby highlighting the ability of the H1N1pdm09 virus to transmit repeatedly from humans to swine, even following adaptive evolution in humans. Similarly, we identified at least 23 separate introductions of human seasonal (non-pandemic) H1 and H3 influenza viruses into swine globally since 1990. Overall, these results reveal the frequency with which swine are exposed to human influenza viruses, indicate that humans make a substantial contribution to the genetic diversity of influenza viruses in swine, and emphasize the need to improve biosecurity measures at the human–swine interface, including influenza vaccination of swine workers.

Sign in / Sign up

Export Citation Format

Share Document