A Novel Computational Tool for Predicting the Human Infectivity of H7N9 Influenza Viruses Isolated from Avian Hosts

The genome composition of a given avian influenza virus is the primary determinant of its potential for cross-species transmission from birds to humans, and acquisition of the ability for human-to-human transmission via gene mutation or reassortment could cause a devastating pandemic. Here we introduce a 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 used the CWBLR model to examine the replication efficiency and pathogenicity of several H7N9 avian isolates that were predicted to have very low or high human infectivity 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.Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (Grant No. 31630079), the National Key R&D Program of China (2016YFD0500206), the National Science and Technology Major Project (2018ZX10101004), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB29010000). W.J.L. is the principal investigator of the Innovative Research Group of National Natural Science Foundation of China (Grant No. 81621091). J.L. is supported by Youth Innovation Promotion Association of CAS (2019091).Declaration of Interests: The authors declare no competing financial interests.Ethics Approval Statement: All experiments using H7N9 subtype strains were conducted in the BSL-3 level laboratory approved by the Wuhan Institute of Virology, Chinese Academy of Sciences. Animal care and housing were in compliance with ethical guidelines and approved by the Experimental Animal Ethic and Welfare Committee of the Institute of Microbiology, Chinese Academy of Sciences.