Istituto Zooprofilattico Sperimentale delle Venezie, Padua, Italy.
J Virol. 2014 Apr;88(8):4375-88. doi: 10.1128/JVI.03181-13. Epub 2014 Feb 5.
Avian influenza (AI) viruses of the H7 subtype have the potential to evolve into highly pathogenic (HP) viruses that represent a major economic problem for the poultry industry and a threat to global health. However, the emergence of HPAI viruses from low-pathogenic (LPAI) progenitor viruses currently is poorly understood. To investigate the origin and evolution of one of the most important avian influenza epidemics described in Europe, we investigated the evolutionary and spatial dynamics of the entire genome of 109 H7N1 (46 LPAI and 63 HPAI) viruses collected during Italian H7N1 outbreaks between March 1999 and February 2001. Phylogenetic analysis revealed that the LPAI and HPAI epidemics shared a single ancestor, that the HPAI strains evolved from the LPAI viruses in the absence of reassortment, and that there was a parallel emergence of mutations among HPAI and later LPAI lineages. Notably, an ultradeep-sequencing analysis demonstrated that some of the amino acid changes characterizing the HPAI virus cluster were already present with low frequency within several individual viral populations from the beginning of the LPAI H7N1 epidemic. A Bayesian phylogeographic analysis revealed stronger spatial structure during the LPAI outbreak, reflecting the more rapid spread of the virus following the emergence of HPAI. The data generated in this study provide the most complete evolutionary and phylogeographic analysis of epidemiologically intertwined high- and low-pathogenicity viruses undertaken to date and highlight the importance of implementing prompt eradication measures against LPAI to prevent the appearance of viruses with fitness advantages and unpredictable pathogenic properties.
The Italian H7 AI epidemic of 1999 to 2001 was one of the most important AI outbreaks described in Europe. H7 viruses have the ability to evolve into HP forms from LP precursors, although the mechanisms underlying this evolutionary transition are only poorly understood. We combined epidemiological information, whole-genome sequence data, and ultradeep sequencing approaches to provide the most complete characterization of the evolution of HPAI from LPAI viruses undertaken to date. Our analysis revealed that the LPAI viruses were the direct ancestors of the HPAI strains and identified low-frequency minority variants with HPAI mutations that were present in the LPAI samples. Spatial analysis provided key information for the design of effective control strategies for AI at both local and global scales. Overall, this work highlights the importance of implementing rapid eradication measures to prevent the emergence of novel influenza viruses with severe pathogenic properties.
H7 亚型禽流感病毒有可能演变成高致病性（HP）病毒，这对家禽业造成了重大的经济问题，并对全球健康构成威胁。然而，低致病性（LPAI）前体病毒演变成 HPAI 病毒的情况目前还了解甚少。为了研究在欧洲描述的最重要的禽流感流行之一的起源和演变，我们调查了在 1999 年 3 月至 2001 年 2 月期间意大利 H7N1 爆发期间收集的 109 株 H7N1（46 株 LPAI 和 63 株 HPAI）病毒的整个基因组的进化和空间动态。系统进化分析显示，LPAI 和 HPAI 流行具有共同的祖先，HPAI 株系是在没有重组的情况下从 LPAI 病毒进化而来的，并且 HPAI 和后来的 LPAI 谱系之间出现了平行的突变。值得注意的是，超深度测序分析表明，在 HPAI 病毒簇中特征氨基酸变化中的一些已经在 LPAI H7N1 流行开始时就以低频率存在于几个个体病毒群体中。贝叶斯系统地理学分析显示，在 LPAI 爆发期间存在更强的空间结构，这反映了 HPAI 出现后病毒传播速度更快。本研究中生成的数据提供了迄今为止对流行病学交织的高致病性和低致病性病毒进行的最完整的进化和系统地理学分析，并强调了实施针对 LPAI 的快速根除措施以防止出现具有适应性优势和不可预测的致病性的病毒的重要性。
1999 年至 2001 年意大利 H7 禽流感流行是欧洲描述的最重要的禽流感流行之一。H7 病毒有能力从 LP 前体进化成 HP 形式，尽管这种进化转变的机制还了解甚少。我们结合了流行病学信息、全基因组序列数据和超深度测序方法，对迄今为止对 HPAI 从 LPAI 病毒进化的最完整描述。我们的分析表明，LPAI 病毒是 HPAI 株系的直接祖先，并确定了在 LPAI 样本中存在具有 HPAI 突变的低频率少数变体。空间分析为在本地和全球范围内设计有效的 AI 控制策略提供了关键信息。总的来说，这项工作强调了实施快速根除措施以防止出现具有严重致病性的新型流感病毒的重要性。
