Publications (36)

  • Article · Oct 2014 · Journal of Clinical Virology
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    Full-text Article · Mar 2013 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology
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    [Show abstract] [Hide abstract] ABSTRACT: Here we report the complete genome sequence of a dengue virus serotype 2 (DENV-2) strain, GZ40, isolated in Guangdong, China, in 2010. A phylogenetic analysis classified GZ40 into the Cosmopolitan genotype, while previous Chinese DENV-2 isolates belong to the Asian I genotype. The reemergence of the Cosmopolitan genotype of DENV-2 in China deserves further investigation.
    Full-text Article · Dec 2012 · Journal of Virology
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    [Show abstract] [Hide abstract] ABSTRACT: We report here the complete genome sequence of a human echovirus type 30 strain ECV30/GX10/05 isolated in Guangxi, China, in 2010. Phylogenetic analysis showed that ECV30/GX10/05 was closely related to a Korean strain isolated in 2008. The sequence information will help in an understanding of the molecular epidemiology and evolution of echovirus.
    Full-text Article · Dec 2012 · Journal of Virology
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    [Show abstract] [Hide abstract] ABSTRACT: Dengue is emerging as the most important mosquito borne viral disease in the world. In mainland China, sporadic and large outbreaks of dengue illness caused by the four serotypes of dengue virus (DENV-1 to DENV-4) have been well documented. Guangdong province is the major affected area in China, and DENV-1 has dominantly circulated in Guangdong for a long time. In this study, a family cluster of DENV-3 infection in Guangzhou was described. Three cases were diagnosed as dengue fever based on clinical manifestation, serological and RT-PCR assays. Two DENV-3 strains were isolated in C6/36 cells and the complete genome sequences were determined. Phylogenetic analysis revealed that the new DENV-3 isolates from the family cluster were grouped within genotype III. Considering the fact that several DENV-3 strains within genotype V were also identified in Guangzhou in 2009, at least two genotypes of DENV-3 co-circulated in Guangzhou. Careful investigation and virological analysis should be warranted in the future.
    Full-text Article · Jun 2012 · Virology Journal
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    [Show abstract] [Hide abstract] ABSTRACT: Figure S1. Phylogenetic tree based on the complete envelope gene from 58 DENV-3 strains by Bayesian method. The evolutionary history was inferred using BEAST 1.7.1 software. The tree was rooted using DENV-1 strain Nauru, DENV-2 strain New Guinea C and DENV-4 strain B5 as outgroups. The newly described DENV-3 isolates in the study are marked with red squares and other Chinese DENV-3 isolates taken for comparison are marked with blue squares. (TIFF 1759 kb)
    Full-text Dataset · Jun 2012
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    [Show abstract] [Hide abstract] ABSTRACT: Here we report the first complete genome sequence of a dengue virus serotype 4 genotype II strain, GZ30, isolated in Guangzhou, Guangdong Province, China, in 2010. The sequence information provided herein will help us to understand the molecular epidemiology of dengue virus and predict the risk of severe diseases in mainland China.
    Full-text Article · Jun 2012 · Journal of Virology
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    Full-text Article · Feb 2012 · Emerging Infectious Diseases
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    [Show abstract] [Hide abstract] ABSTRACT: Similarity scanning and full-length bootscanning analysis of coxsackievirus B (CBV) 5/CC10/10 with other CBV strains and representative enterovirus strains.
    Full-text Dataset · Feb 2012
  • [Show abstract] [Hide abstract] ABSTRACT: Enterovirus type 71 (EV71) causes large outbreaks with significant mortality among young children, and no specific antiviral treatment is currently available. Antibody-based therapy represents a promising alternative strategy for lethal EV71 infection. Our previous data has shown that anti-EV71 neutralization antibodies were present in a significant proportion of blood donors in China. To produce a new human intravenous immunoglobulin (IVIG) product containing high titer anti-EV71 neutralizing antibodies and investigate its therapeutic efficacy against lethal EV71 infection in a murine model. Plasma units that contained high titer neutralizing antibodies from selected Chinese donors were pooled and processed into pharmaceutical grade IVIG preparations according to the standard procedure. The efficacy of these EV71-specific IVIG product was characterized in vitro by neutralization assay and in vivo by suckling mouse protection testing. The therapeutic effects against lethal EV71 challenge were further assayed in a suckling mouse model. About 12% of the normal plasma units were selected and pooled to manufacture the EV71-IVIG preparations, and in vitro and in vivo efficacy data showed that these EV71-specific IVIG preparations were enriched with neutralizing antibodies against EV71. Furthermore, treatment with EV71-specific IVIG was evidenced to confer protection against lethal EV71 challenge in a dose- and time-dependent manner in the suckling mouse model. This preclinical study indicates that these "tailor-made" EV71-IVIG preparations manufactured from selected plasma donors in EV71-endemic areas may represent a promising therapeutic option for the lethal EV71 infections, and further clinical trials should be warranted in the future.
    Article · Jun 2011 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology
  • Article · Feb 2011 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology
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    [Show abstract] [Hide abstract] ABSTRACT: Flaviviruses are a group of human pathogenic, enveloped RNA viruses that includes dengue (DENV), yellow fever (YFV), West Nile (WNV), and Japanese encephalitis (JEV) viruses. Cross-reactive antibodies against Flavivirus have been described, but most of them are generally weakly neutralizing. In this study, a novel monoclonal antibody, designated mAb 2A10G6, was determined to have broad cross-reactivity with DENV 1-4, YFV, WNV, JEV, and TBEV. Phage-display biopanning and structure modeling mapped 2A10G6 to a new epitope within the highly conserved flavivirus fusion loop peptide, the (98)DRXW(101) motif. Moreover, in vitro and in vivo experiments demonstrated that 2A10G6 potently neutralizes DENV 1-4, YFV, and WNV and confers protection from lethal challenge with DENV 1-4 and WNV in murine model. Furthermore, functional studies revealed that 2A10G6 blocks infection at a step after viral attachment. These results define a novel broadly flavivirus cross-reactive mAb with highly neutralizing activity that can be further developed as a therapeutic agent against severe flavivirus infections in humans.
    Full-text Article · Jan 2011 · PLoS ONE
  • [Show abstract] [Hide abstract] ABSTRACT: Dengue viruses (DENVs) are important human pathogens that cause mild dengue fever, and severe dengue hemorrhagic fever/dengue shock syndrome, and no vaccine or antiviral therapy are currently available. At the initial stage of DENV infection, host pattern recognition receptors are responsible for sensing viral proteins or nucleic acids and initiating innate antiviral responses, including the activation of type I interferon (IFN) and proinflammatory cytokines. Two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5), are recently identified as cytoplasmic PPRs for virus infection. Here, in this study the involvement of RIG-I and MDA5 in DENV-induced IFN-β response A549 cells were investigated. DENV infection readily up-regulated RIG-I expression, activated IRF-3 and RIG-I mRNA transcription, and induced the production of IFN-β in A549 cells in a strain- and serotype-independent manner. While gene silencing of RIG-I by small interfering RNAs failed to significantly inhibit IFN-β production induced by DENV infection. Further experiments demonstrated that MDA5 was also induced by DENV infection, and MDA5 knockout did not block DENV induced IFN-β production in A549 cells. Our results demonstrated that both RIG-I and MDA5 were induced but neither of the two was essential for DENV induced IFN IFN-β response in A549 cells. These findings suggest that innate immune pathway are involved in the recognition of DENV by human non-immune cells, and provide insights for the understanding of the molecular mechanism for DENV-induced antiviral response.
    Article · Nov 2010 · Molecular Biology Reports
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    [Show abstract] [Hide abstract] ABSTRACT: Prophylaxis and treatment with oseltamivir effectively controlled a community outbreak of pandemic influenza A (H1N1) in China. The genetic makeup of strains of different generations seemed to be stable. Travel in confined settings might accelerate the transmission of pandemic influenza in a community outbreak.
    Full-text Article · Sep 2010 · Infection Control and Hospital Epidemiology
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    [Show abstract] [Hide abstract] ABSTRACT: Enterovirus 71 (EV71) is an etiologic agent of hand-foot-and-mouth disease (HFMD), and recent HFMD epidemics worldwide have been associated with a severe form of brainstem encephalitis associated with pulmonary edema and high case-fatality rates. EV71 contains a positive-sense single-stranded genome RNA of approximately 7400 bp in length which encodes a polyprotein with a single open reading frame (ORF), which is flanked by untranslated regions at both the 5' and 3' ends. A long distance RT-PCR assay was developed to amplify the full length genome cDNA of EV71 by using specific primes carrying a SP6 promoter. Then the in vitro synthesized RNA transcripts from the RT-PCR amplicons were then transfected into RD cells to produce the rescued virus. The rescued virus was further characterized by RT-PCR and indirect fluorescent-antibody (IFA) assay in comparison with the wild type virus. The rescued viruses were infectious on RD cells and neurovirulent when intracerebrally injected into suckling mice. Thus, we established a rapid method to produce the infectious full length cDNA of EV71 directly from RNA preparations and specific mutations can be easily engineered into the rescued enterovirus genome by this method.
    Full-text Article · Jun 2010 · Virology Journal
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    Full-text Article · Jan 2010 · Clinical Infectious Diseases
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    Full-text Article · Jan 2010 · Clinical Infectious Diseases
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    [Show abstract] [Hide abstract] ABSTRACT: The role of the 3'untranslated region (UTR) of the dengue virus (DENV) genome during viral translation remains to be elucidated. We assessed the contribution of well-defined RNA elements in the 3'UTR of DENV-2 to viral translation using a virus-induced reporting gene system and deoxyribozymes (DRzs) targeting the 3'UTR of the DENV-2 genome. Results show that mRNAs carrying a deletion of repeated conserved sequence (RCS2)-CS2 are translated less efficiently than wild type mRNAs. However, mRNAs with a deletion of CS1-stem loop (SL) are translated more efficiently. Thus, CS1-SL and RCS2-CS2 may have different effects on translational regulation. Additionally, the translation-suppressing effect of CS1-SL or the SL element is further confirmed in DENV-2-infected cells using DRzs. Mutagenesis studies show that, rather than the secondary structure, nucleotides 10663-10677 and 10709-10723 are responsible for translational suppression of SL. Overall, our results demonstrate that sequences and elements within the DENV-2 3'UTR regulate viral translation.
    Full-text Article · Nov 2009 · The American journal of tropical medicine and hygiene
  • [Show abstract] [Hide abstract] ABSTRACT: A pandemic caused by a novel influenza A virus (H1N1) poses a serious public health threat. In this study, a real-time reverse transcriptase PCR (RT-PCR) assay based on the hemagglutinin gene was developed that discriminates the novel H1N1 from swine influenza virus, seasonal H1N1/H3N2 virus and the highly pathogenic H5N1 avian influenza virus. The sensitivity of this assay was 0.2 50% tissue culture infective dose of virus and 200 copies of in vitro-transcribed target RNA. Three hundred and forty-eight clinical specimens from suspected H1N1 patients were tested using this assay, and forty-two (12.07%) were found to be positive. Tests using the real-time PCR assay recommended by WHO and virus isolation gave identical results. This sensitive and specific real-time RT-PCR assay will contribute to the early diagnosis and control of the emerging H1N1 influenza pandemic.
    Article · Oct 2009 · Journal of virological methods
  • [Show abstract] [Hide abstract] ABSTRACT: A full-length cDNA clone (pD212) of dengue virus type 2 isolated in China (DEN2-43) was constructed. Based on this, we constructed several mutants with deletions in capsid protein C using fusion PCR. These deletions removed part or almost all of the internal stretch of hydrophobic amino acid residues that is probably involved in virion assembly. We thus obtained viable mutant viruses. The propagation capacity of the mutant viruses in cell culture was impaired in parallel with the increasing size of the deletion, and the infectivity of mutant C(Delta42-59), from which all of helix III of capsid protein C was removed, was completely abolished. More importantly, the mutant viruses were highly attenuated in suckling mice but induced high levels of antibodies in adult mice. This study indicates that the structural and functional flexibility of capsid protein C make it a candidate target for the attenuation of dengue virus, which could open a promising new avenue for the development of live attenuated dengue vaccines.
    Article · Jul 2007 · Virus Research