References and Notes Supporting Online Material Human Tears Contain a Chemosignal-猫眼课题宝

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G. R. G. B. Webster-G.-R.-G.-B.-Webster-2298068370;E. C. Sharp;Am J Claas;Respir;D. E. Swayne;J. R. Beck;M. L. Perdue;C. W. Beard;C V Hunter;L. S. Tiley;H. M. Sang;J Chen;S. C. Chen;P. Stern;B. B. Scott-B.;C. Lois;S. Tiley;M. Hagen;J. T. Matthews;M. Krystal;J A Van Der Goot;G. Koch;M. C. De Jong;M. van Boven;J L Umbach;H. L. Yen;L. L. Poon-L.;B. R. Cullen;Mbio;F. Thomson;M. Hutchison;S. Gelstein;Y. Yeshurun;L. Rozenkrantz;S. Shushan;Idan Frumin;Y. Roth;N. Sobel

在两只未暴露的对照鸡中。这可能表明抗原或病毒暴露或流产感染。这些数据表明，TG-D5鸡没有有效地将感染传播给与它们一起饲养的禽类，但这种作用的具体机制尚不清楚。聚合酶诱饵可通过直接结合聚合酶或间接影响最近发现的推定调节性小病毒RNA分子的表达水平来破坏复制（14，15）（其也可能在先天免疫中起作用）。尽管诱饵5抑制了细胞培养物中的聚合酶活性，但这并没有转化为从受感染的禽类中的病毒脱落的定量减少（图2）（我们也没有在卵或成纤维细胞培养物中发现任何作用）。聚合酶-RNA相互作用可能参与病毒包装过程，但在细胞培养中通过TG-D5鸡胚成纤维细胞后，我们没有发现对病毒基因组：空斑形成单位比率的任何影响，以支持诱饵诱导缺陷病毒颗粒形成的假设。在胚胎化鸡蛋中单次传代后，测定了从一只TG-D5鸡（#4457，dpi = 2）中排出的病毒的标准静脉内致病性指数，发现其未发生变化，表明通过TG-D5鸡的传代不会快速选择降低排出病毒毒力的稳定遗传变化。我们的目标是证明转基因可以用来预防鸡禽流感感染的原理。TG-D5鸟类明显没有继续传播感染，即使是对与它们直接接触的未受保护（非转基因）鸡也是如此。这一特性可能对鸡群水平的易感性和感染传播产生重大影响，并支持通过遗传修饰控制家禽AIV感染的概念。我们的策略提供了比接种疫苗更大的潜在益处。虽然传统的AIV疫苗可以实现株特异性的临床抵抗主要挑战，无菌免疫不能实现（3）。这种疫苗接种可以使病毒在鸡群中隐蔽循环，促进抗原漂移，并对未接种疫苗的鸟类和与它们接触的人构成风险。相比之下，在TG-D5鸡群水平上不存在向前传播和循环。诱饵5 RNA对应于一个绝对保守的序列，对于调节流感病毒所有亚型的病毒转录、复制和包装至关重要。

in the two unexposed control birds. This may be indicative of antigen or viral exposure or an abortive infection. These data show that the TG-D5 chickens did not efficiently transmit infection to birds housed with them, but the specific mechanism underlying this effect is not known. Polymerase decoys may disrupt replication by direct binding to poly-merase or indirectly by influencing the level of expression of the recently discovered, putative regulatory small viral RNA molecules (14, 15) (which may also have a role in innate immunity). Although decoy 5 suppressed polymerase activity in cell culture, this did not translate into a quantitative reduction in virus shedding from infected birds (Fig. 2) (nor have we found any effect in ovo or in fibroblast cell culture). Polymerase-RNA interactions may be involved in the virus packaging process, but after passage through TG-D5 chick embryo fibroblasts in cell culture, we have not found any effect on the genome:plaque-forming unit ratio of the virus to support the hypothesis that the decoy induced the formation of defective virus particles. The standard intravenous pathogenicity index of the virus shed from one of the TG-D5 chickens (#4457, dpi = 2) was determined after a single passage in embryo-nated hens' eggs and found to be unaltered, indicating that passage through TG-D5 chickens does not rapidly select for a stable genetic change that reduces the virulence of the shed virus. Our goal was a proof-of-principle demonstration that genetic modification can be used to prevent avian influenza infection in chickens. The TG-D5 birds exhibited a marked absence of onward transmission of infection, even to unprotected (nontransgenic) chickens housed in direct contact with them. This property could have a major impact on susceptibility and propagation of infection at the flock level and supports the concept of genetic modification for controlling AIV infection in poultry. Our strategy offers substantial potential benefits over vaccination. Although conventional AIV vaccines can achieve strain-specific clinical resistance to primary challenge , sterile immunity is not achieved (3). Such vaccination can allow the cryptic circulation of virus in flocks, facilitating antigenic drift and posing a risk to unvaccinated birds and humans that come into contact with them. In contrast, onward transmission and circulation at the flock level are absent in the TG-D5 chickens. The decoy 5 RNA corresponds to an absolutely conserved sequence that is essential for the regulation of viral transcription, replication, and packaging of all subtypes of influenza …

References and Notes Supporting Online Material Human Tears Contain a Chemosignal

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