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11.
West Nile virus is a mosquito-borne flavivirus closely related to the human epidemic-causing dengue, yellow fever and Japanese encephalitis viruses. In establishing infection these icosahedral viruses undergo endosomal membrane fusion catalysed by envelope glycoprotein rearrangement of the putative receptor-binding domain III (DIII) and exposure of the hydrophobic fusion loop. Humoral immunity has an essential protective function early in the course of West Nile virus infection. Here, we investigate the mechanism of neutralization by the E16 monoclonal antibody that specifically binds DIII. Structurally, the E16 antibody Fab fragment engages 16 residues positioned on four loops of DIII, a consensus neutralizing epitope sequence conserved in West Nile virus and distinct in other flaviviruses. The E16 epitope protrudes from the surface of mature virions in three distinct environments, and docking studies predict Fab binding will leave five-fold clustered epitopes exposed. We also show that E16 inhibits infection primarily at a step after viral attachment, potentially by blocking envelope glycoprotein conformational changes. Collectively, our results suggest that a vaccine strategy targeting the dominant DIII epitope may elicit safe and effective immune responses against flaviviral diseases. 相似文献
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Why do disused proteins become genetically lost or repressed? 总被引:2,自引:0,他引:2
J M Diamond 《Nature》1986,321(6070):565-566
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Planetary nebulae often have asymmetric shapes, even though their progenitor stars were symmetric; this structure could be the result of collimated jets from the evolved stars before they enter the planetary nebula phase. Theoretical models have shown that magnetic fields could be the dominant source of jet-collimation in evolved stars, just as these fields are thought to collimate outflows in other astrophysical sources, such as active galactic nuclei and proto-stars. But hitherto there have been no direct observations of both the magnetic field direction and strength in any collimated jet. Here we report measurements of the polarization of water vapour masers that trace the precessing jet emanating from the asymptotic giant branch star W43A (at a distance of 2.6 kpc from the Sun), which is undergoing rapid evolution into a planetary nebula. The masers occur in two clusters at opposing tips of the jets, approximately 1,000 au from the star. We conclude from the data that the magnetic field is indeed collimating the jet. 相似文献
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Wang K Diskin SJ Zhang H Attiyeh EF Winter C Hou C Schnepp RW Diamond M Bosse K Mayes PA Glessner J Kim C Frackelton E Garris M Wang Q Glaberson W Chiavacci R Nguyen L Jagannathan J Saeki N Sasaki H Grant SF Iolascon A Mosse YP Cole KA Li H Devoto M McGrady PW London WB Capasso M Rahman N Hakonarson H Maris JM 《Nature》2011,469(7329):216-220
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J M Diamond 《Nature》1999,400(6740):120-121