Institute of Pathogen Biology

Taian, China

Institute of Pathogen Biology

Taian, China
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Ren L.,Ministry of Health Key Laboratory for Systems Biology of Pathogens | Ren L.,Institute of Pathogen Biology | Yu X.,U.S. Center for Disease Control and Prevention | Zhao B.,U.S. Center for Disease Control and Prevention | And 7 more authors.
Emerging Infectious Diseases | Year: 2014

During the early stage of the avian influenza A(H7N9) epidemic in China in March 2013, a strain of the virus was identified in a 4-year-old boy with mild influenza symptoms. Phylogenetic analysis indicated that this strain, which has similarity to avian subtype H9N2 viruses, may represent a precursor of more-evolved H7N9 subtypes co-circulating among humans.


Xiang Z.,MOH Key Laboratory of Systems Biology of Pathogens | Xiang Z.,Institute of Pathogen Biology | Gonzalez R.,Institute of Pathogen Biology | Wang Z.,Institute of Pathogen Biology | And 12 more authors.
Emerging Infectious Diseases | Year: 2012

During August 2006-April 2010, in Beijing, China, 2 rare human enterovirus serotypes, coxsackievirus A21 and enterovirus 68, were detected most frequently in human enterovirus-positive adults with acute respiratory tract infections. Thus, during some years, these 2 viruses cause a substantial proportion of enterovirus-associated adult acute respiratory tract infections.


PubMed | University College Dublin, Institute of Pathogen Biology, Beijing Institute of Microbiology and Epidemiology, Shandong Agricultural University and Dongying Forest and Plant Protection Station
Type: | Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases | Year: 2016

To understand the molecular epidemiology and evolution of avian influenza viruses (AIV) along the East Asian-Australian migration flyway, we collected faecal samples (n=2859) between November 2014 and March 2015 from poultry, environmental sources and wild birds in Dongying, Shandong province and Yancheng, Jiangsu province in eastern China. The presence of AIV RNA was evaluated by real-time PCR and the positivity rate ranged from 0 to 29.3%. In both Dongying and Yancheng, samples collected from live poultry markets had the highest positivity rate for AIV RNA. AIV whole genomes were generated and phylogenetically analysed. Our results demonstrate that most of the viruses belonged to the H9N2 subtype, and could be classified into nine novel genotypes based on the phylogenetic analysis of the eight gene segments of the AIV genomes. This revealed a high genetic diversity of H9N2 in this region and suggested that they might have undergone frequent genetic reassortment. In addition, the internal genes (PB2, etc.) of two viruses from wild birds and several viruses from poultry belonged to the same gene constellation, suggesting a potential inter-host transmission of AIV between wild birds and poultry in live markets along routes of migratory flyways. Our results highlight the high genetic diversity of AIV along the East Asian-Australian migration flyway and the need for more extensive AIV surveillance in eastern China.


PubMed | Institute of Pathogen Biology, Taishan Medical University, University College Dublin, Chinese People's Liberation Army and Beijing Institute of Microbiology and Epidemiology
Type: | Journal: Ticks and tick-borne diseases | Year: 2017

Severe fever with thrombocytopenia syndrome virus (SFTSV) has been continuously circulating in Eastern Asia in recent years, without the availability of effective vaccines or antiviral drugs, posing a serious threat to public health, particularly in the central-eastern provinces of China. In this study, we isolated and sequenced four new SFTSV strains from Shandong Province identified in 2015. Phylogenetic analysis, with all publicly available L, M and S gene segments, revealed that the four newly described SFTSV strains belonged to genotype C3. In addition, our phylogenetic analyses also identified two potentially novel sub-lineages of SFTSV, tentatively named C6 and J4. Our comprehensive analysis revealed twenty recombination events in fourteen SFTSV genomes and recombination events were found in the S gene segment for the first time. A total of twenty-six strains were probable SFTSV reassortants, including sixteen which were previously unidentified. We further characterised the genetic constellation of these putative reassortants and classified them into twelve different reassortment forms. Our study revealed multiple evolutionary forces acting on SFTSV, responsible for the increasing genetic diversity of this agent, which could potentially alter the antigenicity and pathogenicity of the virus. This calls for an urgent need for intensified surveillance and the development of vaccines and antiviral drugs against this high-consequence pathogen.


PubMed | Institute of Pathogen Biology, Chinese Institute of Basic Medical Sciences, Institute for Infectious Disease and Endemic Disease Control, CAS Institute of Microbiology and 2 more.
Type: Journal Article | Journal: Emerging microbes & infections | Year: 2017

We report the first imported case of Rift Valley fever (RVF) in China. The patient returned from Angola, a non-epidemic country, with an infection of a new reassortant from different lineages of Rift Valley fever viruses (RVFVs). The patient developed multiorgan dysfunction and gradually recovered with continuous renal replacement therapy and a short regimen of methylprednisolone treatment. The disordered cytokines and chemokines in the plasma of the patient revealed hypercytokinemia, but the levels of protective cytokines were low upon admission and fluctuated as the disease improved. Whole-genome sequencing and phylogenetic analysis revealed that the imported strain was a reassortant comprising the L and M genes from lineage E and the S gene from lineage A. This case highlights that RVFV had undergone genetic reassortment, which could potentially alter its biological properties, cause large outbreaks and pose a serious threat to global public health as well as the livestock breeding industry.


Bi Y.,CAS Institute of Microbiology | Bi Y.,Chinese Academy of Sciences | Mei K.,CAS Wuhan Institute of Virology | Mei K.,Hubei University | And 15 more authors.
Journal of General Virology | Year: 2015

Eight avian influenza A (H5N6) viruses were isolated from live poultry markets (LPMs) in Sichuan and Jiangxi Provinces in China in 2014, including those close to the county where the human H5N6 infection occurred. Genetic and phylogenetic analyses revealed that these H5N6 viruses were novel reassortants between H5N1 clade 2.3.4 and H6N6 viruses, and had evolved into two distinct lineages (Sichuan and Jiangxi). Moreover, the human H5N6 virus was closely related to the avian-source viruses of Sichuan lineage. Notably, H5N6 viruses contained a T160A substitution in the haemagglutinin protein and an 11 aa deletion in the neuraminidase stalk, which may aid in enhancing viral affinity for human-like receptors and virulence in mammals. As the H5N1 virus infects humans through direct contact, infection with the novel H5N6 virus raised significant concerns that the H5 subtype was a likely candidate for a pandemic. Therefore, extensive and long-term surveillance of avian influenza viruses in LPMs is essential. © 2015 The Authors.


PubMed | Shenzhen Third Peoples Hospital, CAS Wuhan Institute of Virology, Qinghai Lake National Nature Reserve, Novosibirsk State University and 3 more.
Type: Journal Article | Journal: Virologica Sinica | Year: 2016

A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015. Based on the genetic and phylogenetic analyses, the viruses possess a stable gene constellation with a Clade 2.3.2.1c HA, a H9N2-derived PB2 gene and the other six genes of Asian H5N1-origin. The Clade 2.3.2.1c H5N1 reassortants displayed a high genetic relationship to a human H5N1 strain (A/Alberta/01/2014). Further analysis showed that similar viruses have been circulating in wild birds in China, Russia, Dubai (Western Asia), Bulgaria and Romania (Europe), as well as domestic poultry in some regions of Africa. The affected areas include the Central Asian, East Asian-Australasian, West Asian-East African, and Black Sea/Mediterranean flyways. These results show that the novel Clade 2.3.2.1c reassortant viruses are circulating worldwide and may have gained a selective advantage in migratory birds, thus posing a serious threat to wild birds and potentially humans.


Zhou Y.J.,CAS Dalian Institute of Chemical Physics | Zhou Y.J.,University of Chinese Academy of Sciences | Gao W.,Chinese Institute of Materia Medica | Gao W.,Capital Medical University | And 12 more authors.
Journal of the American Chemical Society | Year: 2012

Microbial production can be advantageous over the extraction of phytoterpenoids from natural plant sources, but it remains challenging to rationally and rapidly access efficient pathway variants. Previous engineering attempts mainly focused on the mevalonic acid (MVA) or methyl-d-erythritol phosphate (MEP) pathways responsible for the generation of precursors for terpenoids biosynthesis, and potential interactions between diterpenoids synthases were unexplored. Miltiradiene, the product of the stepwise conversion of (E,E,E)-geranylgeranyl diphosphate (GGPP) catalyzed by diterpene synthases SmCPS and SmKSL, has recently been identified as the precursor to tanshionones, a group of abietane-type norditerpenoids rich in the Chinese medicinal herb Salvia miltiorrhiza. Here, we present the modular pathway engineering (MOPE) strategy and its application for rapid assembling synthetic miltiradiene pathways in the yeast Saccharomyces cerevisiae. We predicted and analyzed the molecular interactions between SmCPS and SmKSL, and engineered their active sites into close proximity for enhanced metabolic flux channeling to miltiradiene biosynthesis by constructing protein fusions. We show that the fusion of SmCPS and SmKSL, as well as the fusion of BTS1 (GGPP synthase) and ERG20 (farnesyl diphosphate synthase), led to significantly improved miltiradiene production and reduced byproduct accumulation. The MOPE strategy facilitated a comprehensive evaluation of pathway variants involving multiple genes, and, as a result, our best pathway with the diploid strain YJ2X reached miltiradiene titer of 365 mg/L in a 15-L bioreactor culture. These results suggest that terpenoids synthases and the precursor supplying enzymes should be engineered systematically to enable an efficient microbial production of phytoterpenoids. © 2012 American Chemical Society.


PubMed | Institute of Pathogen Biology, Chengdu University of Traditional Chinese Medicine and Shandong Agricultural University
Type: Journal Article | Journal: Biological trace element research | Year: 2016

Previous study has demonstrated that mitochondrial-dependent apoptotic pathway is involved in the nephroprotective effect of puerarin (PU) against lead-induced cytotoxicity in primary cultures of rat proximal tubular (rPT) cells. To further clarify how PU exerts its antiapoptotic effects, this study was designed to investigate the role of mitochondrial permeability transition (MPT) and subsequent apoptotic events in the process of PU against Pb-induced cytotoxicity in rPT cells. The results showed that Pb-mediated mitochondrial permeability transition pore (MPTP) opening together with mitochondrial cytochrome c release, activations of caspase-9 and caspase-3, and subsequent poly-ADP-ribose polymerase (PARP) cleavage can be effectively blocked by the addition of PU. Simultaneously, upregulation and downregulation of Bcl-2 and Bax with increased Bcl-2/Bax ratio due to PU administration further alleviated Pb-induced mitochondrial apoptosis. Moreover, PU can reverse Pb-induced ATP depletion by restoring mitochondrial fragmentation to affect ATP production and by regulating expression levels of ANT-1 and ANT-2 to improve ATP transport. In summary, PU produced a significant protection against Pb-induced mitochondrial apoptosis in rPT cells by inhibiting MPTP opening to ameliorate the mitochondrial dysfunction.


PubMed | Institute of Pathogen Biology, Chinese Academy of Agricultural Sciences and Shandong Agricultural University
Type: Journal Article | Journal: BMC veterinary research | Year: 2016

As a typical retrovirus, the evolution of Avian leukosis virus subgroup J (ALV-J) in different infectious ecosystems is not characterized, what we know is there are a cloud of diverse variants, namely quasispecies with considerable genetic diversity. This study is to explore the selection of infectious ecosystems on dominant variants and their evolutionary dynamics of ALV-J between DF1 cells and specific-pathogen-free (SPF) chickens. High-throughput sequencing platforms provide an approach for detecting quasispecies diversity more fully.An average of about 20,000 valid reads were obtained from two variable regions of gp85 gene and LTR-U3 region from each sample in different infectious ecosystems. The top 10 dominant variants among ALV-J from chicken plasmas, DF1 cells and liver tumor were completely different from each other. Also there was a difference of shannon entropy and global selection pressure values () in different infectious ecosystems. In the plasmas of two chickens, a large portion of quasispecies contained a 3-peptides LSD repeat insertion that was only less than 0.01% in DF1 cell culture supernatants. In parallel studies, the LTR-U3 region of ALV-J from the chicken plasmas demonstrated more variants with mutations in their transcription regulatory elements than those from DF1 cells.Our data taken together suggest that the molecular epidemiology based on isolated ALV-J in cell culture may not represent the true evolution of virus in chicken flocks in the field. The biological significance of the LSD insert and mutations in LTR-U3 needs to be further studied.

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