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Xudong Lin - One of the best experts on this subject based on the ideXlab platform.
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the effective rate of influenza Reassortment is limited during human infection
PLOS Pathogens, 2017Co-Authors: Ashley Sobel Leonard, Xudong Lin, Gavin J. D. Smith, David E Wentworth, Rebecca A Halpin, Timothy B Stockwell, Micah T Mcclain, Amy Ransier, Suman R Das, Anthony GilbertAbstract:We characterise the evolutionary dynamics of influenza infection described by viral sequence data collected from two challenge studies conducted in human hosts. Viral sequence data were collected at regular intervals from infected hosts. Changes in the sequence data observed across time show that the within-host evolution of the virus was driven by the reversion of variants acquired during previous passaging of the virus. Treatment of some patients with oseltamivir on the first day of infection did not lead to the emergence of drug resistance variants in patients. Using an evolutionary model, we inferred the effective rate of Reassortment between viral segments, measuring the extent to which randomly chosen viruses within the host exchange genetic material. We find strong evidence that the rate of effective Reassortment is low, such that genetic associations between polymorphic loci in different segments are preserved during the course of an infection in a manner not compatible with epistasis. Combining our evidence with that of previous studies we suggest that spatial heterogeneity in the viral population may reduce the extent to which Reassortment is observed. Our results do not contradict previous findings of high rates of viral Reassortment in vitro and in small animal studies, but indicate that in human hosts the effective rate of Reassortment may be substantially more limited.
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genomewide analysis of Reassortment and evolution of human influenza a h3n2 viruses circulating between 1968 and 2011
Journal of Virology, 2014Co-Authors: Kim B Westgeest, Theo M. Bestebroer, Colin A Russell, Xudong Lin, Monique I J Spronken, Justin Bahl, Ruud Van Beek, Eugene SkepnerAbstract:Influenza A(H3N2) viruses became widespread in humans during the 1968 H3N2 virus pandemic and have been a major cause of influenza epidemics ever since. These viruses evolve continuously by Reassortment and genomic evolution. Antigenic drift is the cause for the need to update influenza vaccines frequently. Using two data sets that span the entire period of circulation of human influenza A(H3N2) viruses, it was shown that influenza A(H3N2) virus evolution can be mapped to 13 antigenic clusters. Here we analyzed the full genomes of 286 influenza A(H3N2) viruses from these two data sets to investigate the genomic evolution and Reassortment patterns. Numerous Reassortment events were found, scattered over the entire period of virus circulation, but most prominently in viruses circulating between 1991 and 1998. Some of these Reassortment events persisted over time, and one of these coincided with an antigenic cluster transition. Furthermore, selection pressures and nucleotide and amino acid substitution rates of all proteins were studied, including those of the recently discovered PB1-N40, PA-X, PA-N155, and PA-N182 proteins. Rates of nucleotide and amino acid substitutions were most pronounced for the hemagglutinin, neuraminidase, and PB1-F2 proteins. Selection pressures were highest in hemagglutinin, neuraminidase, matrix 1, and nonstructural protein 1. This study of genotype in relation to antigenic phenotype throughout the period of circulation of human influenza A(H3N2) viruses leads to a better understanding of the evolution of these viruses.
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genomewide analysis of Reassortment and evolution of human influenza a h3n2 viruses circulating between 1968 and 2011
Journal of Virology, 2014Co-Authors: Kim B Westgeest, Theo M. Bestebroer, Colin A Russell, Xudong Lin, Monique I J Spronken, Justin Bahl, Ruud Van Beek, Eugene SkepnerAbstract:ABSTRACT Influenza A(H3N2) viruses became widespread in humans during the 1968 H3N2 virus pandemic and have been a major cause of influenza epidemics ever since. These viruses evolve continuously by Reassortment and genomic evolution. Antigenic drift is the cause for the need to update influenza vaccines frequently. Using two data sets that span the entire period of circulation of human influenza A(H3N2) viruses, it was shown that influenza A(H3N2) virus evolution can be mapped to 13 antigenic clusters. Here we analyzed the full genomes of 286 influenza A(H3N2) viruses from these two data sets to investigate the genomic evolution and Reassortment patterns. Numerous Reassortment events were found, scattered over the entire period of virus circulation, but most prominently in viruses circulating between 1991 and 1998. Some of these Reassortment events persisted over time, and one of these coincided with an antigenic cluster transition. Furthermore, selection pressures and nucleotide and amino acid substitution rates of all proteins were studied, including those of the recently discovered PB1-N40, PA-X, PA-N155, and PA-N182 proteins. Rates of nucleotide and amino acid substitutions were most pronounced for the hemagglutinin, neuraminidase, and PB1-F2 proteins. Selection pressures were highest in hemagglutinin, neuraminidase, matrix 1, and nonstructural protein 1. This study of genotype in relation to antigenic phenotype throughout the period of circulation of human influenza A(H3N2) viruses leads to a better understanding of the evolution of these viruses. IMPORTANCE Each winter, influenza virus infects approximately 5 to 15% of the world9s population, resulting in significant morbidity and mortality. Influenza A(H3N2) viruses evolve continuously by Reassortment and genomic evolution. This leads to changes in antigenic recognition (antigenic drift) which make it necessary to update vaccines against influenza A(H3N2) viruses frequently. In this study, the relationship of genetic evolution to antigenic change spanning the entire period of A(H3N2) virus circulation was studied for the first time. The results presented in this study contribute to a better understanding of genetic evolution in correlation with antigenic evolution of influenza A(H3N2) viruses.
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genomic Reassortment of influenza a virus in north american swine 1998 2011
Journal of General Virology, 2012Co-Authors: Martha I. Nelson, Xudong Lin, Susan E Detmer, David E Wentworth, Yi Tan, Aaron Schwartzbard, Rebecca A Halpin, Timothy B Stockwell, Amy L Vincent, Marie GramerAbstract:Revealing the frequency and determinants of Reassortment among RNA genome segments is fundamental to understanding basic aspects of the biology and evolution of the influenza virus. To estimate the extent of genomic Reassortment in influenza viruses circulating in North American swine, we performed a phylogenetic analysis of 139 whole-genome viral sequences sampled during 1998–2011 and representing seven antigenically distinct viral lineages. The highest amounts of Reassortment were detected between the H3 and the internal gene segments (PB2, PB1, PA, NP, M and NS), while the lowest Reassortment frequencies were observed among the H1γ, H1pdm and neuraminidase segments, particularly N1. Less Reassortment was observed among specific haemagglutinin–neuraminidase combinations that were more prevalent in swine, suggesting that some genome constellations may be evolutionarily more stable.
Raul Rabadan - One of the best experts on this subject based on the ideXlab platform.
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viral Reassortment as an information exchange between viral segments
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Benjamin Greenbaum, Arnold J Levine, Leo L M Poon, Raul RabadanAbstract:Viruses have an extraordinary ability to diversify and evolve. For segmented viruses, Reassortment can introduce drastic genomic and phenotypic changes by allowing a direct exchange of genetic material between coinfecting strains. For instance, multiple influenza pandemics were caused by Reassortments of viruses typically found in separate hosts. What is unclear, however, are the underlying mechanisms driving these events and the level of intrinsic bias in the diversity of strains that emerge from coinfection. To address this problem, previous experiments looked for correlations between segments of strains that coinfect cells in vitro. Here, we present an information theory approach as the natural mathematical framework for this question. We study, for influenza and other segmented viruses, the extent to which a virus’s segments can communicate strain information across an infection and among one another. Our approach goes beyond previous association studies and quantifies how much the diversity of emerging strains is altered by patterns in Reassortment, whether biases are consistent across multiple strains and cell types, and if significant information is shared among more than two segments. We apply our approach to a new experiment that examines Reassortment patterns between the 2009 H1N1 pandemic and seasonal H1N1 strains, contextualizing its segmental information sharing by comparison with previously reported strain Reassortments. We find evolutionary patterns across classes of experiments and previously unobserved higher-level structures. Finally, we show how this approach can be combined with virulence potentials to assess pandemic threats.
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Reassortment patterns in swine influenza viruses
PLOS ONE, 2009Co-Authors: Hossein Khiabanian, Vladimir Trifonov, Raul RabadanAbstract:Three human influenza pandemics occurred in the twentieth century, in 1918, 1957, and 1968. Influenza pandemic strains are the results of emerging viruses from non-human reservoirs to which humans have little or no immunity. At least two of these pandemic strains, in 1957 and in 1968, were the results of Reassortments between human and avian viruses. Also, many cases of swine influenza viruses have reportedly infected humans, in particular, the recent H1N1 influenza virus of swine origin, isolated in Mexico and the United States. Pigs are documented to allow productive replication of human, avian, and swine influenza viruses. Thus it has been conjectured that pigs are the “mixing vessel” that create the avian-human reassortant strains, causing the human pandemics. Hence, studying the process and patterns of viral Reassortment, especially in pigs, is a key to better understanding of human influenza pandemics. In the last few years, databases containing sequences of influenza A viruses, including swine viruses, collected since 1918 from diverse geographical locations, have been developed and made publicly available. In this paper, we study an ensemble of swine influenza viruses to analyze the Reassortment phenomena through several statistical techniques. The Reassortment patterns in swine viruses prove to be similar to the previous results found in human viruses, both in vitro and in vivo, that the surface glycoprotein coding segments reassort most often. Moreover, we find that one of the polymerase segments (PB1), reassorted in the strains responsible for the last two human pandemics, also reassorts frequently.
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Reassortment patterns in swine influenza viruses
PLOS Currents, 2009Co-Authors: Hossein Khiabanian, Vladimir Trifonov, Raul RabadanAbstract:Previous human influenza pandemics were the results of emerging viruses from non-human reservoirs, with at least two caused by strains of mixed human and avian origin. Also, many cases of swine influenza viruses have reportedly infected humans, including the recent human H1N1 strain, isolated in Mexico and the United States. Pigs are documented to get infected with human, avian, and swine viruses and allow productive replication, thus it has been conjectured that they are the "mixing vessel" that create reassortant strains, causing the human pandemics. In this paper, we apply several statistical techniques to an ensemble of publicly available swine viruses to study the Reassortment phenomena. The Reassortment patterns in swine viruses confirm previous results found in human viruses that the glycoprotein coding segments reassort most often. Moreover, one of the polymerase segments (PB1), reassorted in the strains responsible for the last two human pandemics of 1957 and 1968, also reassorts frequently.
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non random Reassortment in human influenza a viruses
Influenza and Other Respiratory Viruses, 2008Co-Authors: Raul Rabadan, Arnold J Levine, Michael KrasnitzAbstract:Background The influenza A virus has two basic modes of evolution. Because of a high error rate in the process of replication by RNA polymerase, the viral genome drifts via accumulated mutations. The second mode of evolution is termed a shift, which results from the Reassortment of the eight segments of this virus. When two different influenza viruses co-infect the same host cell, new virions can be released that contain segments from both parental strains. This type of shift has been the source of at least two of the influenza pandemics in the 20th century (H2N2 in 1957 and H3N2 in 1968). Objectives The methods to measure these genetic shifts have not yet provided a quantitative answer to questions such as: what is the rate of genetic Reassortment during a local epidemic? Are all possible Reassortments equally likely or are there preferred patterns? Methods To answer these questions and provide a quantitative way to measure genetic shifts, a new method for detecting Reassortments from nucleotide sequence data was created that does not rely upon phylogenetic analysis. Two different sequence databases were used: human H3N2 viruses isolated in New York State between 1995 and 2006, and human H3N2 viruses isolated in New Zealand between 2000 and 2005. Results Using this new method, we were able to reproduce all the Reassortments found in earlier works, as well as detect, with very high confidence, many Reassortments that were not detected by previous authors. We obtain a lower bound on the Reassortment rate of 2–3 events per year, and find a clear preference for Reassortments involving only one segment, most often hemagglutinin or neuraminidase. At a lower frequency several segments appear to reassort in vivo in defined groups as has been suggested previously in vitro. Conclusions Our results strongly suggest that the patterns of Reassortment in the viral population are not random. Deciphering these patterns can be a useful tool in attempting to understand and predict possible influenza pandemics.
Anice C Lowen - One of the best experts on this subject based on the ideXlab platform.
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influenza a virus Reassortment is limited by anatomical compartmentalization following coinfection via distinct routes
Journal of Virology, 2017Co-Authors: Mathilde Richard, Sander Herfst, Hui Tao, Nathan T Jacobs, Anice C LowenAbstract:Exchange of gene segments through Reassortment is a major feature of influenza A virus evolution and frequently contributes to the emergence of novel epidemic, pandemic, and zoonotic strains. It has long been evident that viral diversification through Reassortment is constrained by genetic incompatibility between divergent parental viruses. In contrast, the role of virus-extrinsic factors in determining the likelihood of Reassortment has remained unclear. To evaluate the impact of such factors in the absence of confounding effects of segment mismatch, we previously reported an approach in which Reassortment between wild-type (wt) and genetically tagged variant (var) viruses of the same strain is measured. Here, using wt/var systems in the A/Netherlands/602/2009 (pH1N1) and A/Panama/2007/99 (H3N2) strain backgrounds, we tested whether inoculation of parental viruses into distinct sites within the respiratory tract limits their Reassortment. Using a ferret (Mustella putorius furo) model, either matched parental viruses were coinoculated intranasally or one virus was instilled intranasally whereas the second was instilled intratracheally. Dual intranasal inoculation resulted in robust Reassortment for wt/var viruses of both strain backgrounds. In contrast, when infections were initiated simultaneously at distinct sites, strong compartmentalization of viral replication was observed and minimal Reassortment was detected. The observed lack of viral spread between upper and lower respiratory tract tissues may be attributable to localized exclusion of superinfection within the host, mediated by innate immune responses. Our findings indicate that dual infections in nature are more likely to result in Reassortment if viruses are seeded into similar anatomical locations and have matched tissue tropisms.IMPORTANCE Genetic exchange between influenza A viruses (IAVs) through Reassortment can facilitate the emergence of antigenically drifted seasonal strains and plays a prominent role in the development of pandemics. Typical human influenza infections are concentrated in the upper respiratory tract; however, lower respiratory tract (LRT) infection is an important feature of severe cases, which are more common in the very young, the elderly, and individuals with underlying conditions. In addition to host factors, viral characteristics and mode of transmission can also increase the likelihood of LRT infection: certain zoonotic IAVs are thought to favor the LRT, and transmission via small droplets allows direct seeding into lower respiratory tract tissues. To gauge the likelihood of Reassortment in coinfected hosts, we assessed the extent to which initiation of infection at distinct respiratory tract sites impacts Reassortment frequency. Our results reveal that spatially distinct inoculations result in anatomical compartmentalization of infection, which in turn strongly limits Reassortment.
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constraints drivers and implications of influenza a virus Reassortment
Annual Review of Virology, 2017Co-Authors: Anice C LowenAbstract:Influenza A viruses are constantly changing. This change accounts for seasonal epidemics, infrequent pandemics, and zoonotic outbreaks. A major mechanism underlying the genetic diversification of influenza A virus is Reassortment of intact gene segments between coinfecting viruses. This exchange is possible because of the segmented nature of the viral genome. Here, I first consider the constraints and drivers acting on influenza A virus Reassortment, including the likelihood of coinfection at the host and cellular levels, mixing and assembly of heterologous gene segments within coinfected cells, and the fitness associated with reassortant genotypes. I then discuss the implications of Reassortment for influenza A virus evolution, including its classically recognized role in the emergence of genetically "shifted" pandemic strains as well as its potential role as a catalyst of genetic drift.
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influenza virus Reassortment is enhanced by semi infectious particles but can be suppressed by defective interfering particles
PLOS Pathogens, 2015Co-Authors: Judith M Fonville, Nicolle Marshall, John Steel, Hui Tao, Anice C LowenAbstract:A high particle to infectivity ratio is a feature common to many RNA viruses, with ~90–99% of particles unable to initiate a productive infection under low multiplicity conditions. A recent publication by Brooke et al. revealed that, for influenza A virus (IAV), a proportion of these seemingly non-infectious particles are in fact semi-infectious. Semi-infectious (SI) particles deliver an incomplete set of viral genes to the cell, and therefore cannot support a full cycle of replication unless complemented through co-infection. In addition to SI particles, IAV populations often contain defective-interfering (DI) particles, which actively interfere with production of infectious progeny. With the aim of understanding the significance to viral evolution of these incomplete particles, we tested the hypothesis that SI and DI particles promote diversification through Reassortment. Our approach combined computational simulations with experimental determination of infection, co-infection and Reassortment levels following co-inoculation of cultured cells with two distinct influenza A/Panama/2007/99 (H3N2)-based viruses. Computational results predicted enhanced Reassortment at a given % infection or multiplicity of infection with increasing semi-infectious particle content. Comparison of experimental data to the model indicated that the likelihood that a given segment is missing varies among the segments and that most particles fail to deliver ≥1 segment. To verify the prediction that SI particles augment Reassortment, we performed co-infections using viruses exposed to low dose UV. As expected, the introduction of semi-infectious particles with UV-induced lesions enhanced Reassortment. In contrast to SI particles, inclusion of DI particles in modeled virus populations could not account for observed Reassortment outcomes. DI particles were furthermore found experimentally to suppress detectable Reassortment, relative to that seen with standard virus stocks, most likely by interfering with production of infectious progeny from co-infected cells. These data indicate that semi-infectious particles increase the rate of Reassortment and may therefore accelerate adaptive evolution of IAV.
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influenza a virus Reassortment
Current Topics in Microbiology and Immunology, 2014Co-Authors: John Steel, Anice C LowenAbstract:Reassortment is the process by which influenza viruses swap gene segments. This genetic exchange is possible due to the segmented nature of the viral genome and occurs when two differing influenza viruses co-infect a cell. The viral diversity generated through Reassortment is vast and plays an important role in the evolution of influenza viruses. Herein we review recent insights into the contribution of Reassortment to the natural history and epidemiology of influenza A viruses, gained through population scale phylogenic analyses. We describe methods currently used to study Reassortment in the laboratory, and we summarize recent progress made using these experimental approaches to further our understanding of influenza virus Reassortment and the contexts in which it occurs.
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influenza virus Reassortment occurs with high frequency in the absence of segment mismatch
PLOS Pathogens, 2013Co-Authors: Nicolle Marshall, Lalita Priyamvada, Zachary Ende, John Steel, Anice C LowenAbstract:Reassortment is fundamental to the evolution of influenza viruses and plays a key role in the generation of epidemiologically significant strains. Previous studies indicate that Reassortment is restricted by segment mismatch, arising from functional incompatibilities among components of two viruses. Additional factors that dictate the efficiency of Reassortment remain poorly characterized. Thus, it is unclear what conditions are favorable for Reassortment and therefore under what circumstances novel influenza A viruses might arise in nature. Herein, we describe a system for studying Reassortment in the absence of segment mismatch and exploit this system to determine the baseline efficiency of Reassortment and the effects of infection dose and timing. Silent mutations were introduced into A/Panama/2007/99 virus such that high-resolution melt analysis could be used to differentiate all eight segments of the wild-type and the silently mutated variant virus. The use of phenotypically identical parent viruses ensured that all progeny were equally fit, allowing Reassortment to be measured without selection bias. Using this system, we found that Reassortment occurred efficiently (88.4%) following high multiplicity infection, suggesting the process is not appreciably limited by intracellular compartmentalization. That co-infection is the major determinant of Reassortment efficiency in the absence of segment mismatch was confirmed with the observation that the proportion of viruses with reassortant genotypes increased exponentially with the proportion of cells co-infected. The number of reassortants shed from co-infected guinea pigs was likewise dependent on dose. With 106 PFU inocula, 46%–86% of viruses isolated from guinea pigs were reassortants. The introduction of a delay between infections also had a strong impact on Reassortment and allowed definition of time windows during which super-infection led to Reassortment in culture and in vivo. Overall, our results indicate that Reassortment between two like influenza viruses is efficient but also strongly dependent on dose and timing of the infections.
Eugene Skepner - One of the best experts on this subject based on the ideXlab platform.
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genomewide analysis of Reassortment and evolution of human influenza a h3n2 viruses circulating between 1968 and 2011
Journal of Virology, 2014Co-Authors: Kim B Westgeest, Theo M. Bestebroer, Colin A Russell, Xudong Lin, Monique I J Spronken, Justin Bahl, Ruud Van Beek, Eugene SkepnerAbstract:Influenza A(H3N2) viruses became widespread in humans during the 1968 H3N2 virus pandemic and have been a major cause of influenza epidemics ever since. These viruses evolve continuously by Reassortment and genomic evolution. Antigenic drift is the cause for the need to update influenza vaccines frequently. Using two data sets that span the entire period of circulation of human influenza A(H3N2) viruses, it was shown that influenza A(H3N2) virus evolution can be mapped to 13 antigenic clusters. Here we analyzed the full genomes of 286 influenza A(H3N2) viruses from these two data sets to investigate the genomic evolution and Reassortment patterns. Numerous Reassortment events were found, scattered over the entire period of virus circulation, but most prominently in viruses circulating between 1991 and 1998. Some of these Reassortment events persisted over time, and one of these coincided with an antigenic cluster transition. Furthermore, selection pressures and nucleotide and amino acid substitution rates of all proteins were studied, including those of the recently discovered PB1-N40, PA-X, PA-N155, and PA-N182 proteins. Rates of nucleotide and amino acid substitutions were most pronounced for the hemagglutinin, neuraminidase, and PB1-F2 proteins. Selection pressures were highest in hemagglutinin, neuraminidase, matrix 1, and nonstructural protein 1. This study of genotype in relation to antigenic phenotype throughout the period of circulation of human influenza A(H3N2) viruses leads to a better understanding of the evolution of these viruses.
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genomewide analysis of Reassortment and evolution of human influenza a h3n2 viruses circulating between 1968 and 2011
Journal of Virology, 2014Co-Authors: Kim B Westgeest, Theo M. Bestebroer, Colin A Russell, Xudong Lin, Monique I J Spronken, Justin Bahl, Ruud Van Beek, Eugene SkepnerAbstract:ABSTRACT Influenza A(H3N2) viruses became widespread in humans during the 1968 H3N2 virus pandemic and have been a major cause of influenza epidemics ever since. These viruses evolve continuously by Reassortment and genomic evolution. Antigenic drift is the cause for the need to update influenza vaccines frequently. Using two data sets that span the entire period of circulation of human influenza A(H3N2) viruses, it was shown that influenza A(H3N2) virus evolution can be mapped to 13 antigenic clusters. Here we analyzed the full genomes of 286 influenza A(H3N2) viruses from these two data sets to investigate the genomic evolution and Reassortment patterns. Numerous Reassortment events were found, scattered over the entire period of virus circulation, but most prominently in viruses circulating between 1991 and 1998. Some of these Reassortment events persisted over time, and one of these coincided with an antigenic cluster transition. Furthermore, selection pressures and nucleotide and amino acid substitution rates of all proteins were studied, including those of the recently discovered PB1-N40, PA-X, PA-N155, and PA-N182 proteins. Rates of nucleotide and amino acid substitutions were most pronounced for the hemagglutinin, neuraminidase, and PB1-F2 proteins. Selection pressures were highest in hemagglutinin, neuraminidase, matrix 1, and nonstructural protein 1. This study of genotype in relation to antigenic phenotype throughout the period of circulation of human influenza A(H3N2) viruses leads to a better understanding of the evolution of these viruses. IMPORTANCE Each winter, influenza virus infects approximately 5 to 15% of the world9s population, resulting in significant morbidity and mortality. Influenza A(H3N2) viruses evolve continuously by Reassortment and genomic evolution. This leads to changes in antigenic recognition (antigenic drift) which make it necessary to update vaccines against influenza A(H3N2) viruses frequently. In this study, the relationship of genetic evolution to antigenic change spanning the entire period of A(H3N2) virus circulation was studied for the first time. The results presented in this study contribute to a better understanding of genetic evolution in correlation with antigenic evolution of influenza A(H3N2) viruses.
Weifeng Shi - One of the best experts on this subject based on the ideXlab platform.
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the first imported case of rift valley fever in china reveals a genetic Reassortment of different viral lineages
Emerging microbes & infections, 2017Co-Authors: Jingyuan Liu, Weifeng Shi, Yulan Sun, Shuguang Tan, Yang Pan, Shujuan Cui, Qingchao Zhang, Xiangfeng Dou, Lijuan Chen, Chuansong QuanAbstract:The first imported case of Rift Valley fever in China reveals a genetic Reassortment of different viral lineages
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dynamic Reassortments and genetic heterogeneity of the human infecting influenza a h7n9 virus
Nature Communications, 2014Co-Authors: Lunbiao Cui, Di Liu, Weifeng Shi, Jingcao Pan, Xiling Guo, Minghao Zhou, Joel Haywood, Haixia Xiao, Kangchen Zhao, Yefei ZhuAbstract:Influenza A (H7N9) virus has been causing human infections in China since February 2013, raising serious concerns of potential pandemics. Previous studies demonstrate that human infection is directly linked to live animal markets, and that the internal genes of the virus are derived from H9N2 viruses circulating in the Yangtze River Delta area in Eastern China. Here following analysis of 109 viruses, we show a much higher genetic heterogeneity of the H7N9 viruses than previously reported, with a total of 27 newly designated genotypes. Phylogenetic and genealogical inferences reveal that genotypes G0 and G2.6 dominantly co-circulate within poultry, with most human isolates belonging to the genotype G0. G0 viruses are also responsible for the inter- and intra-province transmissions, leading to the genesis of novel genotypes. These observations suggest the province-specific H9N2 virus gene pools increase the genetic diversity of H7N9 via dynamic Reassortments and also imply that G0 has not gained overwhelming fitness and the virus continues to undergo Reassortment.
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prospective of genomics in revealing transmission Reassortment and evolution of wildlife borne avian influenza a h5n1 viruses
Current Genomics, 2011Co-Authors: Fumin Lei, Weifeng ShiAbstract:The outbreak of highly pathogenic avian influenza (HPAI) H5N1 disease has led to significant loss of poultry and wild life and case fatality rates in humans of 60%. Wild birds are natural hosts for all avian influenza virus subtypes and over120 bird species have been reported with evidence of H5N1 infection. Influenza A viruses possess a segmented RNA genome and are characterized by frequently occurring genetic Reassortment events, which play a very important role in virus evolution and the spread of novel gene constellations in immunologically naive human and animal populations. Phylogenetic analysis of whole genome or sub-genomic sequences is a standard means for delineating genetic variation, novel Reassortment events, and surveillance to trace the global transmission pathways. In this paper, special emphasis is given to the transmission and circulation of H5N1 among wild life populations, and to the Reassortment events that are associated with inter-host transmission of the H5N1 viruses when they infect different hosts, such as birds, pigs and humans. In addition, we review the inter-subtype Reassortment of the viral segments encoding inner proteins between the H5N1 viruses and viruses of other subtypes, such as H9N2 and H6N1. Finally, we highlight the usefulness of genomic sequences in molecular epidemiological analysis of HPAI H5N1 and the technical limitations in existing analytical methods that hinder them from playing a greater role in virological research.
