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Tong Y.-G.,State Key Laboratory of Pathogen and Biosecurity | Shi W.-F.,Institute of Pathogen Biology | Liu D.,CAS Institute of Microbiology | Qian J.,Key Laboratory of Jilin Province for Zoonosis Prevention and Control | And 53 more authors.
Nature | Year: 2015

A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 × 10 â '3 substitutions per site per year (95% highest posterior density interval, 1.04 × 10 â '3 to 1.41 × 10 â '3 substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics. © 2015 Macmillan Publishers Limited. All rights reserved.


Ye Q.,Beijing Institute of Microbiology and Epidemiology | Liu Z.-Y.,Beijing Institute of Microbiology and Epidemiology | Han J.-F.,Beijing Institute of Microbiology and Epidemiology | Jiang T.,Beijing Institute of Microbiology and Epidemiology | And 5 more authors.
Infection, Genetics and Evolution | Year: 2016

The rapid spread and potential link with birth defects have made Zika virus (ZIKV) a global public health problem. The virus was discovered 70 years ago, yet the knowledge about its genomic structure and the genetic variations associated with current ZIKV explosive epidemics remains not fully understood. In this review, the genome organization, especially conserved terminal structures of ZIKV genome were characterized and compared with other mosquito-borne flaviviruses. It is suggested that major viral proteins of ZIKV share high structural and functional similarity with other known flaviviruses as shown by sequence comparison and prediction of functional motifs in viral proteins. Phylogenetic analysis demonstrated that all ZIKV strains circulating in the America form a unique clade within the Asian lineage. Furthermore, we identified a series of conserved amino acid residues that differentiate the Asian strains including the current circulating American strains from the ancient African strains. Overall, our findings provide an overview of ZIKV genome characterization and evolutionary dynamics in the Americas and point out critical clues for future virological and epidemiological studies. © 2016 Elsevier B.V.


Lu H.-J.,Key Laboratory of Jilin Province for Zoonosis Prevention and Control | Qian J.,Key Laboratory of Jilin Province for Zoonosis Prevention and Control | Kargbo D.,Ministry of Health and Sanitation | Zhang X.-G.,U.S. Center for Disease Control and Prevention | And 18 more authors.
Emerging Infectious Diseases | Year: 2015

During 2014–2015, an outbreak of Ebola virus disease (EVD) swept across parts of West Africa. The China Mobile Laboratory Testing Team was dispatched to support response efforts, during September 28–November 11, 2014, they conducted PCR testing on samples from 1,635 suspected EVD patients. Of those patients, 50.4% were positive, of whom 84.6% lived within a 3-km zone along main roads connecting rural towns and densely populated cities. The median time from symptom onset to testing was 5 days. At testing, 75.7% of the confirmed patients had fever, and 94.1% reported at least 1 gastrointestinal symptom, all symptoms, except rash and hemorrhage, were more frequent in confirmed than nonconfirmed patients. Virus loads were significantly higher in EVD patients with fever, diarrhea, fatigue, or headache. The case-fatality rate was lower among patients 15–44 years of age and with virus loads of <100,000 RNA copies/mL. These findings are key for optimizing EVD control and treatment measures. © 2015, Centers for Disease Control and Prevention (CDC). All rights reserved.


Lee C.M.,Novartis | Xie X.,Novartis | Zou J.,Novartis | Zou J.,CAS Wuhan Institute of Virology | And 9 more authors.
Journal of Virology | Year: 2015

Flavivirus NS4A protein induces host membrane rearrangement and functions as a replication complex component. The molecular details of how flavivirus NS4A exerts these functions remain elusive. Here, we used dengue virus (DENV) as a model to characterize and demonstrate the biological relevance of flavivirus NS4A oligomerization. DENV type 2 (DENV-2) NS4A protein forms oligomers in infected cells or when expressed alone. Deletion mutagenesis mapped amino acids 50 to 76 (spanning the first transmembrane domain [TMD1]) of NS4A as the major determinant for oligomerization, while the N-terminal 50 residues contribute only slightly to the oligomerization. Nuclear magnetic resonance (NMR) analysis of NS4A amino acids 17 to 80 suggests that residues L31, L52, E53, G66, and G67 could participate in oligomerization. Ala substitution for 15 flavivirus conserved NS4A residues revealed that these amino acids are important for viral replication. Among the 15 mutated NS4A residues, 2 amino acids (E50A and G67A) are located within TMD1. Both E50A and G67A attenuated viral replication, decreased NS4A oligomerization, and reduced NS4A protein stability. In contrast, NS4A oligomerization was not affected by the replication-defective mutations (R12A, P49A, and K80A) located outside TMD1. trans complementation experiments showed that expression of wild-type NS4A alone was not sufficient to rescue the replication-lethal NS4A mutants. However, the presence of DENV-2 replicons could partially restore the replication defect of some lethal NS4A mutants (L26A and K80A), but not others (L60A and E122A), suggesting an unidentified mechanism governing the outcome of complementation in a mutant-dependent manner. Collectively, the results have demonstrated the importance of TMD1-mediated NS4A oligomerization in flavivirus replication. © 2015, American Society for Microbiology.


PubMed | Chinese PLA General Hospital, University of Washington, State Key Laboratory of Pathogen and Biosecurity and Beijing Institute of Microbiology and Epidemiology
Type: Journal Article | Journal: PloS one | Year: 2017

We developed a dynamic forecasting model for Zika virus (ZIKV), based on real-time online search data from Google Trends (GTs). It was designed to provide Zika virus disease (ZVD) surveillance and detection for Health Departments, and predictive numbers of infection cases, which would allow them sufficient time to implement interventions. In this study, we found a strong correlation between Zika-related GTs and the cumulative numbers of reported cases (confirmed, suspected and total cases; p<0.001). Then, we used the correlation data from Zika-related online search in GTs and ZIKV epidemics between 12 February and 20 October 2016 to construct an autoregressive integrated moving average (ARIMA) model (0, 1, 3) for the dynamic estimation of ZIKV outbreaks. The forecasting results indicated that the predicted data by ARIMA model, which used the online search data as the external regressor to enhance the forecasting model and assist the historical epidemic data in improving the quality of the predictions, are quite similar to the actual data during ZIKV epidemic early November 2016. Integer-valued autoregression provides a useful base predictive model for ZVD cases. This is enhanced by the incorporation of GTs data, confirming the prognostic utility of search query based surveillance. This accessible and flexible dynamic forecast model could be used in the monitoring of ZVD to provide advanced warning of future ZIKV outbreaks.


Qian Q.,State Key Laboratory of Pathogen and Biosecurity | Qian Q.,Institute of Health Service and Medical Information | Zhao J.,U.S. Center for Disease Control and Prevention | Fang L.,State Key Laboratory of Pathogen and Biosecurity | And 7 more authors.
BMC Infectious Diseases | Year: 2014

Background: Qinghai-Tibetan Plateau of China is known to be the plague endemic region where marmot (Marmota himalayana) is the primary host. Human plague cases are relatively low incidence but high mortality, which presents unique surveillance and public health challenges, because early detection through surveillance may not always be feasible and infrequent clinical cases may be misdiagnosed.Methods: Based on plague surveillance data and environmental variables, Maxent was applied to model the presence probability of plague host. 75% occurrence points were randomly selected for training model, and the rest 25% points were used for model test and validation. Maxent model performance was measured as test gain and test AUC. The optimal probability cut-off value was chosen by maximizing training sensitivity and specificity simultaneously.Results: We used field surveillance data in an ecological niche modeling (ENM) framework to depict spatial distribution of natural foci of plague in Qinghai-Tibetan Plateau. Most human-inhabited areas at risk of exposure to enzootic plague are distributed in the east and south of the Plateau. Elevation, temperature of land surface and normalized difference vegetation index play a large part in determining the distribution of the enzootic plague.Conclusions: This study provided a more detailed view of spatial pattern of enzootic plague and human-inhabited areas at risk of plague. The maps could help public health authorities decide where to perform plague surveillance and take preventive measures in Qinghai-Tibetan Plateau. © 2014 Qian et al.


PubMed | Institute of Pathogen Biology, U.S. Center for Disease Control and Prevention, State Key Laboratory of Pathogen and Biosecurity, Chinese National Institute for Viral Disease Control and Prevention and CAS Institute of Microbiology
Type: Journal Article | Journal: mBio | Year: 2015

The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory tract infection with a high fatality rate in humans. Coronaviruses are capable of infecting multiple species and can evolve rapidly through recombination events. Here, we report the complete genomic sequence analysis of a MERS-CoV strain imported to China from South Korea. The imported virus, provisionally named ChinaGD01, belongs to group 3 in clade B in the whole-genome phylogenetic tree and also has a similar tree topology structure in the open reading frame 1a and -b (ORF1ab) gene segment but clusters with group 5 of clade B in the tree constructed using the S gene. Genetic recombination analysis and lineage-specific single-nucleotide polymorphism (SNP) comparison suggest that the imported virus is a recombinant comprising group 3 and group 5 elements. The time-resolved phylogenetic estimation indicates that the recombination event likely occurred in the second half of 2014. Genetic recombination events between group 3 and group 5 of clade B may have implications for the transmissibility of the virus.The recent outbreak of MERS-CoV in South Korea has attracted global media attention due to the speed of spread and onward transmission. Here, we present the complete genome of the first imported MERS-CoV case in China and demonstrate genetic recombination events between group 3 and group 5 of clade B that may have implications for the transmissibility of MERS-CoV.


Xue R.-D.,Anastasia Mosquito Control District | Qualls W.A.,Anastasia Mosquito Control District | Kline D.L.,U.S. Department of Agriculture | Zhao T.-Y.,State Key Laboratory of Pathogen and Biosecurity
Journal of the American Mosquito Control Association | Year: 2010

Field evaluation of Lurex 3™, 1-octen-3-ol (octenol), and CO 2 sachet as baits in Mosquito Magnet® Pro traps (MMP) for collecting adult mosquitoes was conducted at 2 different locations in northeast Florida. A total of 18 species of mosquitoes were collected by the MMP baited with the 3 attractant baits in St. Augustine, FL. The MMP baited with octenol collected significantly more mosquitoes than the traps baited with Lurex 3 and the CO2 sachet. A total of 6 floodwater mosquito species were collected by the MMP baited with the 3 attractant baits in Elkton, FL. The MMP baited with Lurex 3 or octenol collected more mosquitoes than the MMP baited with CO2 sachet or MMP alone. © 2010 by The American Mosquito Control Association, Inc.


PubMed | 307th Hospital of PLA, University of Science and Technology of China and State Key Laboratory of Pathogen and Biosecurity
Type: Journal Article | Journal: Genome announcements | Year: 2016

We report here the first complete genome of Serratia rubidaea, isolated from a patient in China.

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