Department of Infection Biology, University of Liverpool, Leahurst Campus, Neston, Cheshire CH64 7TE, UK.
J Gen Virol. 2011 Feb;92(Pt 2):346-54. doi: 10.1099/vir.0.026740-0. Epub 2010 Nov 3.
Previously, a virulent avian metapneumovirus, farm isolate Italy 309/04, was shown to have been derived from a live vaccine. Virulence due to the five nucleotide mutations associated with the reversion to virulence was investigated by their addition to the genome of the vaccine strain using reverse genetics. Virulence of these recombinant viruses was determined by infection of 1-day-old turkeys. Disease levels resulting from the combined two matrix mutations was indistinguishable from that produced by the recombinant vaccine, whereas the combined three L gene mutations increased disease to a level (P<0.0001) that was indistinguishable from that caused by the revertant Italy 309/04 virus. Testing of the L mutations individually showed that two mutations did not increase virulence, while the third mutation, corresponding to an asparagine to aspartic acid substitution, produced virulence indistinguishable from that caused by Italy 309/04. In contrast to the vaccine, the virulent mutant also showed increased viability at temperatures typical of turkey core tissues. The notion that increased viral virulence resulted from enhanced ability to replicate in tissues away from the cool respiratory tract, cannot be discounted.
先前，一种强毒禽偏肺病毒，即意大利 309/04 分离株，被证实源自活疫苗。通过反向遗传学，将与毒力恢复相关的 5 个核苷酸突变添加到疫苗株的基因组中，从而研究了这些突变导致的毒力。通过感染 1 日龄火鸡来确定这些重组病毒的毒力。由两个基质突变联合引起的疾病水平与重组疫苗产生的疾病水平无法区分，而三个 L 基因突变联合则使疾病加重至与意大利 309/04 病毒引起的疾病水平无法区分（P<0.0001）。单独测试 L 突变表明，两个突变不会增加毒力，而第三个突变，即对应天冬酰胺到天冬氨酸的取代，产生的毒力与意大利 309/04 病毒引起的毒力无法区分。与疫苗不同的是，强毒突变株在火鸡核心组织中典型的温度下也表现出更高的存活能力。不能排除病毒毒力增加是由于在远离凉爽的呼吸道的组织中复制能力增强的观点。
