Genome sequences of haemagglutinin cleavage site predict the pathogenicity phenotype of avian influenza virus: statistically validated data for facilitating rapid declarations and reducing reliance on <i>in vivo</i> testing
收藏资源简介：
Based on the pathogenicity in chickens, most H1–H16 avian influenza viruses (AIV) cause mild diseases, whereas some of the H5 and H7 AI viruses cause severe, systemic disease. The number of basic amino acids in the haemagglutinin (HA) cleavage site of AIV plays a critical role in pathogenicity. As we gain a greater understanding of the molecular mechanisms of pathogenicity, genome sequencing of the HA0 cleavage site has assumed a greater role in assessment of the potential pathogenicity of H5 and H7 viruses. We validated the use of HA cleavage site motif analysis by comparing molecular pathotyping data against experimental <i>in vivo</i> (intravenous pathogenicity index [IVPI] and lethality) data for determination of both low pathogenicity and high pathogenicity AI virus declaration with the goal of expediting pathotype confirmation and further reducing the reliance on <i>in vivo</i> testing. Our data provide statistical support to the continued use of molecular determination of pathotype for AI viruses based on the HA cleavage site sequence in the absence of an <i>in vivo</i> study determination. This approach not only expedites the declaration process of highly pathogenic AIV (HPAIV) but also reduces the need for experimental <i>in vivo</i> testing of H5 and H7 viruses.
基于鸡的致病性特征，绝大多数H1~H16亚型禽流感病毒（AIV）仅引发轻度病症，而部分H5和H7亚型禽流感病毒则可导致严重的全身性疾病。禽流感病毒血凝素（HA）裂解位点的碱性氨基酸数量对其致病性起着关键作用。随着对致病性分子机制的认知不断深化，HA0裂解位点的基因组序列测定在评估H5和H7亚型病毒潜在致病性中的重要性日益凸显。本研究通过对比分子致病型鉴定数据与体内（in vivo）实验获得的静脉致病指数（IVPI）及致死性数据，验证了血凝素裂解位点基序分析的应用价值，旨在快速确认病毒致病型、进一步减少体内实验依赖，以完成低致病性与高致病性禽流感病毒的判定。本研究数据为：在缺乏体内实验判定结果的前提下，基于血凝素裂解位点序列开展的禽流感病毒致病型分子鉴定方法的持续应用提供了统计学支持。该方法不仅可加快高致病性禽流感病毒（HPAIV）的判定流程，还能降低针对H5和H7亚型病毒开展体内实验的需求。
