CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, Virginia, USA.
Transbound Emerg Dis. 2021 Mar;68(2):846-856. doi: 10.1111/tbed.13750. Epub 2020 Aug 8.
The genome composition of a given avian influenza virus is the primary determinant of its potential for cross-species transmission from birds to humans. Here, we introduce a viral genome-based computational tool that can be used to evaluate the human infectivity of avian isolates of influenza A H7N9 viruses, which can enable prediction of the potential risk of these isolates infecting humans. This tool, which is based on a novel class weight-biased logistic regression (CWBLR) algorithm, uses the sequences of the eight genome segments of an H7N9 strain as the input and gives the probability of this strain infecting humans (reflecting its human infectivity). We examined the replication efficiency and the pathogenicity of several H7N9 avian isolates that were predicted to have very low or high human infectivity by the CWBLR model in cell culture and in mice, and found that the strains with high predicted human infectivity replicated more efficiently in mammalian cells and were more infective in mice than those that were predicted to have low human infectivity. These results demonstrate that our CWBLR model can serve as a powerful tool for predicting the human infectivity and cross-species transmission risks of H7N9 avian strains.
给定的禽流感病毒的基因组构成是其从鸟类向人类跨物种传播潜力的主要决定因素。在这里，我们引入了一种基于病毒基因组的计算工具，可用于评估甲型 H7N9 禽流感病毒的禽类分离株对人类的感染性，从而能够预测这些分离株感染人类的潜在风险。该工具基于一种新型类权重偏置逻辑回归（CWBLR）算法，使用 H7N9 株的八个基因组片段的序列作为输入，并给出该株感染人类的概率（反映其对人类的感染性）。我们在细胞培养和小鼠中检查了几种被 CWBLR 模型预测为具有极低或高人类感染性的 H7N9 禽源分离株的复制效率和致病性，发现预测具有高人类感染性的分离株在哺乳动物细胞中的复制效率更高，并且比预测具有低人类感染性的分离株更具感染性。这些结果表明，我们的 CWBLR 模型可以作为预测 H7N9 禽源株的人类感染性和跨物种传播风险的有力工具。
