Origin and generation of verogenic Newcastle disease viruses

一种良性新城疫病毒（NDV）最近在家鸡中复制时变得具有高度毒力。目前尚不清楚在野生水禽中传播的NDVs是否也有可能在鸡中成为高致病性（速度性）。为了从实验上证明非致病性水禽分离物产生速度性NDV，我们在鸡中传代了一种无毒的鹅分离物。通过气囊接种连续九代，然后在鸡脑中接种五代后，病毒在鸡中变得具有高度毒性，产生100%的死亡率，并在致病性测试中显示出典型的速度特性。融合蛋白裂解位点的序列分析表明，原分离物含有典型的无毒型序列E-R-Q-E-R/L，在鸡体内的重复传代过程中，该序列逐渐发展为典型的毒型序列K-R-Q-K-R/F。这些结果表明，在野生水禽中存在且具有一致的无毒型序列的无毒病毒，在鸡群中传播和传播后具有速度性。结果还表明，鸡提供了一种从无毒背景中选择毒性病毒的机制。

A benign Newcastle disease virus(NDV) recently became highly virulent during replication in domestic chickens. It is still unclear whether NDVs circulating among wild waterfowl also have the potential to become highly pathogenic (velogenic) in chickens. To demonstrate experimentally the generation of velogenic NDV from a nonpathogenic waterfowl isolate, we passaged an avirulent goose isolate in chickens. After nine consecutive passages by air-sac inoculation, followed by five passages in chick brain, the virus became highly virulent in chickens, producing a 100% mortality rate, and demonstrating typical velogenic properties in pathogenicity tests. Sequence analysis at the fusion protein cleavage site showed that the original isolate contained the typical avirulent type sequence, E-R-Q-E-R/L, which progressed incrementally to a typical virulent type, K-R-Q-K-R/F, during repeated passage in chickens. These results demonstrate that avirulent viruses, maintained in wild waterfowl in nature and bearing the consensus avirulent type sequence, have the potential to become velogenic after transmission to and circulation in chicken populations. The results also suggest that chickens provide a mechanism for the selection of virulent viruses from an avirulent background.