News Article | November 2, 2016
ORLANDO, Fla. — New evidence from separate labs supports the controversial idea that an overlooked and unexpected Culex mosquito might spread Zika virus. The southern house mosquito, Culex quinquefasciatus, is common in the Americas. Constância Ayres, working with Brazil’s Oswaldo Cruz Foundation in Recife, previously surprised Zika researchers with the disturbing proposal that this mosquito might be a stealth spreader of Zika. But two U.S. research groups tested the basic idea and couldn’t get the virus to infect the species. Now, preliminary results from Ayres’ and two other research groups are renewing the discussion. The data, shared September 26 at the International Congress of Entomology, suggest that Zika can build up in the house mosquito’s salivary glands — a key step in being able to transmit disease. Basic insect physiology is only part of the puzzle, though. Even if the mosquitoes prove competent at passing along Zika, there remain questions of whether their tastes, behavior and ecology will lead them to actually do so. In the current outbreak, the World Health Organization has focused on mosquitoes in a different genus, Aedes, particularly Ae. aegypti, as the main disease vector. But Ayres had announced months ago the discovery of the virus in Brazil’s free-flying house mosquitoes (SN Online: 7/28/16). At the congress, Ayres’ foundation colleague Duschinka Guedes reported that captive mosquitoes fed Zika-tainted blood had virus growing in their own guts and salivary glands within days. The virus doesn’t spread every time a mosquito slurping contaminated blood gets virus smeared on its mouthparts, though. To move from the mosquito to what it bites, viruses have to infect the insect midgut, then travel to the salivary glands and build up enough of a population for an infective dose drooling into the next victim. When Guedes offered the infected mosquitoes a special card to bite, they left telltale virus in the salivary traces, a sign of what they could do when biting — and infecting — a real animal. Researchers from China and Canada who were not originally on the symposium program also stepped up to share their results, some of which are unpublished. Some tasks are still in early stages, but both labs showed Zika virus building up in some kind of Culex mosquitoes. At the Beijing Institute of Microbiology and Epidemiology, Tong-Yan Zhao found the virus peaking in the house mosquitoes eight days after their first contaminated drink. As a test of the infectious powers of the mosquitoes, researchers let the Zika-carrying insects bite baby lab mice. Later, the virus showed up in the brains of eight out of nine lab mice. The results were reported September 7 in Emerging Microbes & Infections. From Brock University in St. Catharines, Canada, Fiona Hunter has found signs that 11 out of 50 wild-caught Culex pipiens pipiens mosquitoes picked up the virus somewhere on their bodies. So far, she has completely analyzed one mosquito and reports that the virus was indeed in its saliva. These positive results contradict Culex tests at the University of Texas Medical Branch in Galveston. Those tests, with U.S. mosquitoes, found no evidence that C. quinquefasciatus can pick up and pass along a Zika infection, says study coauthor Scott Weaver. Stephen Higgs of Kansas State University in Manhattan and his colleagues got similar results. “We’re pretty good at infecting mosquitoes,” Higgs says, so he muses over whether certain virus strains won’t infect mosquitoes from particular places. The main risk from Culex at the moment is distraction, warned Roger Nasci of North Shore Mosquito Abatement District in Northfield, Ill. After the talks, he rose from the audience to say that Ae. aegypti is a known enemy and limited resources should not be diverted from fighting it. George Peck, who runs mosquito control for Clackamas County in Oregon, isn’t convinced that the high virus concentrations dosing the test mosquitoes are realistic. Yet he’s watching the issue because like much of northern North America, Clackamas doesn’t have the Ae. aegypti vector to worry about. But it does have plenty of Culex mosquitoes. Editor’s note: This story was updated September 30, 2016, to add information relating to Zhao’s study.
Chen S.P.,Beijing Institute of Microbiology and Epidemiology
Epidemiology and Infection | Year: 2012
We elucidated the molecular epidemiology and evolution of Japanese encephalitis virus (JEV) strains isolated from 1949 to 2009 in China in this study. Three genotypes (I, III, V) were confirmed to be co-circulating in China in both high-and low-prevalence areas. Genotype III consisted of two clades (mainland clade and Taiwan clade). Compared to the mainland clade, genotype I and the Taiwan clade were newly introduced and evolved more rapidly. We also demonstrated that JEV strains in China, especially those in the mainland clade, were not only under purifying selection, but also probably under positive selection (aa 227 and 408 in the envelope protein). © 2011 Cambridge University Press.
Yan Y.,Beijing Institute of Microbiology and Epidemiology
PloS one | Year: 2013
Small non-coding RNAs (sRNAs) facilitate host-microbe interactions. They have a central function in the post-transcriptional regulation during pathogenic lifestyles. Hfq, an RNA-binding protein that many sRNAs act in conjunction with, is required for Y. pestis pathogenesis. However, information on how Yersinia pestis modulates the expression of sRNAs during infection is largely unknown. We used RNA-seq technology to identify the sRNA candidates expressed from Y. pestis grown in vitro and in the infected lungs of mice. A total of 104 sRNAs were found, including 26 previously annotated sRNAs, by searching against the Rfam database with 78 novel sRNA candidates. Approximately 89% (93/104) of these sRNAs from Y. pestis are shared with its ancestor Y. pseudotuberculosis. Ninety-seven percent of these sRNAs (101/104) are shared among more than 80 sequenced genomes of 135 Y. pestis strains. These 78 novel sRNAs include 62 intergenic and 16 antisense sRNAs. Fourteen sRNAs were selected for verification by independent Northern blot analysis. Results showed that nine selected sRNA transcripts were Hfq-dependent. Interestingly, three novel sRNAs were identified as new members of the transcription factor CRP regulon. Semi-quantitative analysis revealed that Y. pestis from the infected lungs induced the expressions of six sRNAs including RyhB1, RyhB2, CyaR/RyeE, 6S RNA, RybB and sR039 and repressed the expressions of four sRNAs, including CsrB, CsrC, 4.5S RNA and sR027. This study is the first attempt to subject RNA from Y. pestis-infected samples to direct high-throughput sequencing. Many novel sRNAs were identified and the expression patterns of relevant sRNAs in Y. pestis during in vitro growth and in vivo infection were revealed. The annotated sRNAs accounted for the most abundant sRNAs either expressed in bacteria grown in vitro or differentially expressed in the infected lungs. These findings suggested these sRNAs may have important functions in Y. pestis physiology or pathogenesis.
Cao R.Y.,Beijing Institute of Microbiology and Epidemiology
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology | Year: 2011
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. Copyright © 2011 Elsevier B.V. All rights reserved.
Sun S.,Beijing Institute of Microbiology and Epidemiology
PloS one | Year: 2011
Fulminant hepatic failure (FHF) is a clinically severe type of liver injury with an extremely high mortality rate. Although the pathological mechanisms of FHF are not well understood, evidence suggests that the complement system is involved in the pathogenesis of a variety of liver disorders. In the present study, to investigate the role of complement in FHF, we examined groups of mice following intraperitoneal injection of LPS/D-GalN: wild-type C57BL/6 mice, wild-type mice treated with a C3aR antagonist, C5aR monoclonal antibody (C5aRmAb) or CR2-Factor H (CR2-fH, an inhibitor of the alternative pathway), and C3 deficient mice (C3-/- mice). The animals were euthanized and samples analyzed at specific times after LPS/D-GalN injection. The results show that intraperitoneal administration of LPS/D-GalN activated the complement pathway, as evidenced by the hepatic deposition of C3 and C5b-9 and elevated serum levels of the complement activation product C3a, the level of which was associated with the severity of the liver damage. C3a receptor (C3aR) and C5a receptor (C5aR) expression was also upregulated. Compared with wild-type mice, C3-/- mice survived significantly longer and displayed reduced liver inflammation and attenuated pathological damage following LPS/D-GalN injection. Similar levels of protection were seen in mice treated with C3aR antagonist,C5aRmAb or CR2-fH. These data indicate an important role for the C3a and C5a generated by the alternative pathway in LPS/D-GalN-induced FHF. The data further suggest that complement inhibition may be an effective strategy for the adjunctive treatment of fulminant hepatic failure.
Chen S.,Beijing Institute of Microbiology and Epidemiology
Infection, Genetics and Evolution | Year: 2011
Phylogenetic analysis suggested that the DENV1 strains isolated in the DF outbreak in Guangdong province in 2006 were likely to be imported from Southeast Asian. Specifically, viruses isolated from Shantou and Chaozhou were imported from Singapore; viruses isolated from Guangzhou, Yangjiang, and Foshan were imported from Thailand/Vietnam. Therefore, importation of DENV1 from Southeast Asia was an important contributory factor of the 2006 DF outbreak in Guangdong province. © 2011 Elsevier B.V.
Li L.,Beijing Institute of Microbiology and Epidemiology
AIDS research and human retroviruses | Year: 2012
Zhengzhou is the capital of Henan province, where severe HIV prevalence was found in former paid plasma donors. In recent years, the HIV epidemic in men who have sex with men (MSM) increased rapidly in the city. To explore the subtype distribution and genetic characterization of HIV in MSM in Zhengzhou city, phylogenetic analysis was fulfilled based on the full-length gag, pol, and partial env gene. A total of 31 HIV-1-seropositive MSM individuals were enrolled. The full length gag, pol, and partial env gene were amplified and sequenced. Multiple subtypes, including CRF01_AE (45.2%), subtype B (38.7%), and CRF07_BC (16.1%), were identified. Close phylogenetic relationships among our strains with strains from the Henan local area, Hebei MSM population, Beijing area, and Liaoning area were found, suggesting a multiple introduction of HIV into the population. The results will provide clues for prevention and for changes in behavior in the Henan MSM population and also detailed sequence data for vaccine design.
Chen S.P.,Beijing Institute of Microbiology and Epidemiology
Epidemiology and Infection | Year: 2013
Thailand was a hyper-endemic country for dengue with co-circulation of four serotypes and tens of thousands of infected cases annually. Taking into consideration the large number of local dengue virus (DENV) sequences available in GenBank, Thailand was the most ideal locality to study co-evolution of DENV. Therefore, we undertook a large-scale molecular epidemiological analysis of all DENV strains isolated in Thailand. In this study, we demonstrated that DENV strains of four serotypes post-1990 grouped into distinct clades, and that specific mutations in the envelope protein were first confirmed in these clades. Compared to the DENV1, DENV2 and DENV3 clades, the DENV4 clade evolved markedly more slowly (6·4 × 10-5 substitutions/site per year). Our results also showed that the genetic diversity of the predominant genotype of each serotype tended to slightly increase over time with fluctuating changes, followed by a stationary phase after 2000. This suggests that the four DENV clades became the predominant strains due to DENV possessing improved fitness after long-term selection. © 2012 Cambridge University Press.
Agency For Science, Novartis, Beijing Institute of Microbiology and Epidemiology | Date: 2013-09-23
The present invention discloses a method of eliciting an immune response and a method of vaccination comprising administration of a mutated flavivirus. The mutated flavivirus comprises at least one mutation in a nucleic acid sequence encoding for the non-structural protein 5 of the flavivirus sequence resulting in inactivation of the 2O-methyltransferase.
Li H.-Y.,CAS Institut Pasteur of Shanghai |
Han J.-F.,Beijing Institute of Microbiology and Epidemiology |
Qin C.-F.,Beijing Institute of Microbiology and Epidemiology |
Chen R.,CAS Institut Pasteur of Shanghai
Vaccine | Year: 2013
Human Enterovirus 71 (EV71) is recognized as the leading causative agent of hand-foot-and-mouth disease (HFMD) in the Asia-Pacific region in recent years. There are still no approved antiviral drugs or vaccines against EV71 infection yet. In this study, we have developed an advanced platform for production of the virus-like particles (VLPs) for EV71 in Saccharomyces Cerevisiae by co-expressing P1 and 3CD genes of EV71. These VLPs exhibited similar morphology and protein composition as EV71 empty particles produced from EV71-infected cells. Immunization with VLPs in mice elicited robust neutralization antibodies against EV71 and potent cellular immune response. In vivo challenge experiments showed that the immune sera induced by VLP conferred protection in neonate mice against lethal EV71 challenge. Together, our study indicated that VLP from yeast is another potential vaccine candidate against EV71 infection. © 2013 Elsevier Ltd.