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Author

Xinchun Chen

Bio: Xinchun Chen is an academic researcher. The author has contributed to research in topics: Influenza A virus & Influenza A virus subtype H5N1. The author has an hindex of 5, co-authored 6 publications receiving 764 citations.

Papers
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Journal ArticleDOI
10 Oct 2013-Nature
TL;DR: It is shown that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions and subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7n7 lineage.
Abstract: A novel H7N9 influenza A virus first detected in March 2013 has since caused more than 130 human infections in China, resulting in 40 deaths. Preliminary analyses suggest that the virus is a reassortant of H7, N9 and H9N2 avian influenza viruses, and carries some amino acids associated with mammalian receptor binding, raising concerns of a new pandemic. However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully known. Using a combination of active surveillance, screening of virus archives, and evolutionary analyses, here we show that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions. We show that the H7 viruses subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at live poultry markets, which are thought to be the immediate source of human infections. Whether the H7N9 outbreak lineage has, or will, become enzootic in China and neighbouring regions requires further investigation. The discovery here of a related H7N7 influenza virus in chickens that has the ability to infect mammals experimentally, suggests that H7 viruses may pose threats beyond the current outbreak. The continuing prevalence of H7 viruses in poultry could lead to the generation of highly pathogenic variants and further sporadic human infections, with a continued risk of the virus acquiring human-to-human transmissibility.

420 citations

Journal ArticleDOI
04 Jun 2015-Nature
TL;DR: It is shown that H7N9 viruses have spread from eastern to southern China and become persistent in chickens, which has led to the establishment of multiple regionally distinct lineages with different reassortant genotypes.
Abstract: Since 2013 the occurrence of human infections by a novel avian H7N9 influenza virus in China has demonstrated the continuing threat posed by zoonotic pathogens. Although the first outbreak wave that was centred on eastern China was seemingly averted, human infections recurred in October 2013 (refs 3-7). It is unclear how the H7N9 virus re-emerged and how it will develop further; potentially it may become a long-term threat to public health. Here we show that H7N9 viruses have spread from eastern to southern China and become persistent in chickens, which has led to the establishment of multiple regionally distinct lineages with different reassortant genotypes. Repeated introductions of viruses from Zhejiang to other provinces and the presence of H7N9 viruses at live poultry markets have fuelled the recurrence of human infections. This rapid expansion of the geographical distribution and genetic diversity of the H7N9 viruses poses a direct challenge to current disease control systems. Our results also suggest that H7N9 viruses have become enzootic in China and may spread beyond the region, following the pattern previously observed with H5N1 and H9N2 influenza viruses.

194 citations

Journal ArticleDOI
TL;DR: Wang et al. as discussed by the authors found that over 50% of pigs tested were seropositive for one or more H1 influenza viruses, most commonly pdm/09-like viruses.
Abstract: Pigs are considered to be intermediate hosts and "mixing vessels," facilitating the genesis of pandemic influenza viruses, as demonstrated by the emergence of the 2009 H1N1 pandemic (pdm/09) virus The prevalence and repeated introduction of the pdm/09 virus into pigs raises the possibility of generating novel swine influenza viruses with the potential to infect humans To address this, an active influenza surveillance program was conducted with slaughtered pigs in abattoirs in southern China Over 50% of the pigs tested were found to be seropositive for one or more H1 influenza viruses, most commonly pdm/09-like viruses Out of 36 virus isolates detected, one group of novel reassortants had Eurasian avian-like swine H1N1 surface genes and pdm/09 internal genes Animal experiments showed that this virus transmitted effectively from pig to pig and from pig to ferret, and it could also replicate in ex vivo human lung tissue Immunization against the 2009 pandemic virus gave only partial protection to ferrets The continuing prevalence of the pdm/09 virus in pigs could lead to the genesis of novel swine reassortant viruses with the potential to infect humans

83 citations

Journal ArticleDOI
TL;DR: From extensive surveillance of SIVs over a 38-month period in southern China, it was found that although neither complete pdm/09 viruses nor their surface genes could persist in pigs, their internal genes did persist and became predominant, potentially replacing those of the enzootic SIV lineages.
Abstract: Two-way transmission of influenza viruses between humans and swine has been frequently observed, and the occurrence of the 2009 H1N1 pandemic influenza virus (pdm/09) demonstrated that swine-origin viruses could facilitate the genesis of a pandemic strain. Although multiple introductions to and reassortment in swine of the pdm/09 virus have been repeatedly reported in both Eurasia and the Americas, its long-term impact on the development of swine influenza viruses (SIVs) has not been systematically explored. Our comprehensive evolutionary studies of the complete genomes of 387 SIVs obtained from 2009 to 2012 by influenza virus surveillance in China revealed 17 reassortant genotypes with pdm/09-origin genes. Even though the entire 2009 pandemic virus and its surface genes cannot persist, its internal genes have become established and are now the predominant lineages in pigs in the region. The main persistent pdm/09-origin reassortant forms had at least five pdm/09-origin internal genes, and their surface genes were primarily of European avian-like (EA) or human H3N2-like SIV origin. These findings represent a marked change in the evolutionary patterns and ecosystem of SIVs in China. It is possible that the pdm/09-origin internal genes are in the process of replacing EA or triple-reassortant-like internal genes. These alterations in the SIV gene pool need to be continually monitored to assess changes in the potential for SIV transmission to humans. IMPORTANCE Shortly after the emergence of the 2009 pandemic H1N1 (pdm/09) influenza virus, it was transmitted from humans to pigs and this continues to occur around the world. Many reassortants between pdm/09-origin viruses and enzootic swine influenza viruses (SIVs) have been detected. However, the long-term impact of pdm/09-origin viruses on the SIV gene pool, which could lead to the generation of influenza viruses with the potential to infect humans, has not been systematically examined. From extensive surveillance of SIVs over a 38-month period in southern China, it was found that although neither complete pdm/09 viruses nor their surface genes could persist in pigs, their internal genes did persist. Over the survey period, these internal genes became predominant, potentially replacing those of the enzootic SIV lineages. The altered diversity of the SIV gene pool needs to be closely monitored for changes in the potential for SIV transmission to humans.

79 citations

Journal ArticleDOI
TL;DR: This is the first evidence that swine reassortant viruses with pdm/09-like genes may have become established in the field, altering the landscape of human and swine influenza.
Abstract: The 2009 pandemic influenza virus (pdm/09) has been frequently introduced to pigs and has reassorted with other swine viruses. Recently, H3N2 reassortants with pdm/09-like internal genes were isolated in Guangxi and Hong Kong, China. Genetic and epidemiological analyses suggest that these viruses have circulated in swine for some time. This is the first evidence that swine reassortant viruses with pdm/09-like genes may have become established in the field, altering the landscape of human and swine influenza.

60 citations


Cited by
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Journal ArticleDOI
TL;DR: An r package, ggtree, which provides programmable visualization and annotation of phylogenetic trees, which can read more tree file formats than other softwares, and support visualization of phylo, multiphylo, phylo4, phyla4d, obkdata and phyloseq tree objects defined in other r packages.
Abstract: Summary We present an r package, ggtree, which provides programmable visualization and annotation of phylogenetic trees. ggtree can read more tree file formats than other softwares, including newick, nexus, NHX, phylip and jplace formats, and support visualization of phylo, multiphylo, phylo4, phylo4d, obkdata and phyloseq tree objects defined in other r packages. It can also extract the tree/branch/node-specific and other data from the analysis outputs of beast, epa, hyphy, paml, phylodog, pplacer, r8s, raxml and revbayes software, and allows using these data to annotate the tree. The package allows colouring and annotation of a tree by numerical/categorical node attributes, manipulating a tree by rotating, collapsing and zooming out clades, highlighting user selected clades or operational taxonomic units and exploration of a large tree by zooming into a selected portion. A two-dimensional tree can be drawn by scaling the tree width based on an attribute of the nodes. A tree can be annotated with an associated numerical matrix (as a heat map), multiple sequence alignment, subplots or silhouette images. The package ggtree is released under the artistic-2.0 license. The source code and documents are freely available through bioconductor (http://www.bioconductor.org/packages/ggtree).

2,692 citations

Journal ArticleDOI
01 Jan 2016-Science
TL;DR: Camels serve as an important reservoir for the maintenance and diversification of the MERS-CoVs and are the source of human infections with this virus, according to surveillance in Saudi Arabia in 2014 and 2015.
Abstract: Outbreaks of Middle East respiratory syndrome (MERS) raise questions about the prevalence and evolution of the MERS coronavirus (CoV) in its animal reservoir. Our surveillance in Saudi Arabia in 2014 and 2015 showed that viruses of the MERS-CoV species and a human CoV 229E-related lineage co-circulated at high prevalence, with frequent co-infections in the upper respiratory tract of dromedary camels. viruses of the betacoronavirus 1 species, we found that dromedary camels share three CoV species with humans. Several MERS-CoV lineages were present in camels, including a recombinant lineage that has been dominant since December 2014 and that subsequently led to the human outbreaks in 2015. Camels therefore serve as an important reservoir for the maintenance and diversification of the MERS-CoVs and are the source of human infections with this virus.

373 citations

Journal ArticleDOI
TL;DR: Recent data on the interaction between influenza virus HA and SA receptors of the host, and the impact on virus host range, pathogenesis, and transmission are reviewed and remaining challenges and future research priorities are discussed.
Abstract: The recent emergence of a novel avian A/H7N9 influenza virus in poultry and humans in China, as well as laboratory studies on adaptation and transmission of avian A/H5N1 influenza viruses, has shed new light on influenza virus adaptation to mammals. One of the biological traits required for animal influenza viruses to cross the species barrier that received considerable attention in animal model studies, in vitro assays, and structural analyses is receptor binding specificity. Sialylated glycans present on the apical surface of host cells can function as receptors for the influenza virus hemagglutinin (HA) protein. Avian and human influenza viruses typically have a different sialic acid (SA)-binding preference and only few amino acid changes in the HA protein can cause a switch from avian to human receptor specificity. Recent experiments using glycan arrays, virus histochemistry, animal models, and structural analyses of HA have added a wealth of knowledge on receptor binding specificity. Here, we review recent data on the interaction between influenza virus HA and SA receptors of the host, and the impact on virus host range, pathogenesis, and transmission. Remaining challenges and future research priorities are also discussed.

336 citations

Journal ArticleDOI
12 Jul 2013-Science
TL;DR: A ferret model was used to evaluate the infectivity and transmissibility of A/Shanghai/2/2013 (SH2), a human H7N9 virus isolate, which showed limited capacity for airborne infectivity but efficiently transmitted between ferrets via direct contact, but less efficiently by airborne exposure.
Abstract: The emergence of the H7N9 influenza virus in humans in Eastern China has raised concerns that a new influenza pandemic could occur. Here, we used a ferret model to evaluate the infectivity and transmissibility of A/Shanghai/2/2013 (SH2), a human H7N9 virus isolate. This virus replicated in the upper and lower respiratory tracts of the ferrets and was shed at high titers for 6 to 7 days, with ferrets showing relatively mild clinical signs. SH2 was efficiently transmitted between ferrets via direct contact, but less efficiently by airborne exposure. Pigs were productively infected by SH2 and shed virus for 6 days but were unable to transmit the virus to naive pigs or ferrets. Under appropriate conditions, human-to-human transmission of the H7N9 virus may be possible.

278 citations

Journal ArticleDOI
TL;DR: Over more than 10 y of cocirculation of multiple H9N2 genotypes, a “fittest” genotype emerged with changed antigenicity and improved adaptability in chickens that became predominant in vaccinated farm chickens in China and caused widespread outbreaks before the H7N9 virus emergence.
Abstract: The emergence of human infection with a novel H7N9 influenza virus in China raises a pandemic concern. Chicken H9N2 viruses provided all six of the novel reassortant’s internal genes. However, it is not fully understood how the prevalence and evolution of these H9N2 chicken viruses facilitated the genesis of the novel H7N9 viruses. Here we show that over more than 10 y of cocirculation of multiple H9N2 genotypes, a genotype (G57) emerged that had changed antigenicity and improved adaptability in chickens. It became predominant in vaccinated farm chickens in China, caused widespread outbreaks in 2010–2013 before the H7N9 viruses emerged in humans, and finally provided all of their internal genes to the novel H7N9 viruses. The prevalence and variation of H9N2 influenza virus in farmed poultry could provide an important early warning of the emergence of novel reassortants with pandemic potential.

267 citations