Computational Biology; Metagenomics; Metatranscriptomics; Next-generation sequencing; Bacterial antibiotic resistance

Representative Research Achievements

(1)Game animals are wildlife species traded and consumed as food and are potential reservoirs for SARS-CoV and SARS-CoV-2. We performed a meta-transcriptomic analysis of 1,941 game animals, representing 18 species and five mammalian orders, sampled across China. From this, we identified 102 mammalian-infecting viruses, with 65 described for the first time. Twenty-one viruses were considered as potentially high risk to humans and domestic animals. Civets (Paguma larvata) carried the highest number of potentially high-risk viruses. We inferred the transmission of bat-associated coronavirus from bats to civets, as well as cross-species jumps of coronaviruses from bats to hedgehogs, from birds to porcupines, and from dogs to raccoon dogs. Of note, we identified avian Influenza A virus H9N2 in civets and Asian badgers, with the latter displaying respiratory symptoms, as well as cases of likely human-to-wildlife virus transmission. These data highlight the importance of game animals as potential drivers of disease emergence.

(2)The ongoing SARS (severe acute respiratory syndrome)-CoV (coronavirus)-2 pandemic has exposed major gaps in our knowledge on the origin, ecology, evolution, and spread of animal coronaviruses. Porcine epidemic diarrhea virus (PEDV) is a member of the genus Alphacoronavirus in the family Coronaviridae that may have originated from bats and leads to significant hazards and widespread epidemics in the swine population. The role of local and global trade of live swine and swine-related products in disseminating PEDV remains unclear, especially in developing countries with complex swine production systems. Here, we undertake an in-depth phylogeographic analysis of PEDV sequence data (including 247 newly sequenced samples) and employ an extension of this inference framework that enables formally testing the contribution of a range of predictor variables to the geographic spread of PEDV. Within China, the provinces of Guangdong and Henan were identified as primary hubs for the spread of PEDV, for which we estimate live swine trade to play a very important role. On a global scale, the United States and China maintain the highest number of PEDV lineages. We estimate that, after an initial introduction out of China, the United States acted as an important source of PEDV introductions into Japan, Korea, China, and Mexico. Live swine trade also explains the dispersal of PEDV on a global scale. Given the increasingly global trade of live swine, our findings have important implications for designing prevention and containment measures to combat a wide range of livestock coronaviruses.

(3)The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown once again that coronavirus (CoV) in animals are potential sources for epidemics in humans. Porcine deltacoronavirus (PDCoV) is an emerging enteropathogen of swine with a worldwide distribution. Here, we implemented and described an approach to analyze the epidemiology of PDCoV following its emergence in the pig population. We performed an integrated analysis of full genome sequence data from 21 newly sequenced viruses, along with comprehensive epidemiological surveillance data collected globally over the last 15 years. We found four distinct phylogenetic lineages of PDCoV, which differ in their geographic circulation patterns. Interestingly, we identified more frequent intra- and interlineage recombination and higher virus genetic diversity in the Chinese lineages compared with the USA lineage where pigs are raised in different farming systems and ecological environments. Most recombination breakpoints are located in the ORF1ab gene rather than in genes encoding structural proteins. We also identified five amino acids under positive selection in the spike protein suggesting a role for adaptive evolution. According to structural mapping, three positively selected sites are located in the N-terminal domain of the S1 subunit, which is the most likely involved in binding to a carbohydrate receptor, whereas the other two are located in or near the fusion peptide of the S2 subunit and thus might affect membrane fusion. Finally, our phylogeographic investigations highlighted notable South-North transmission as well as frequent long-distance dispersal events in China that could implicate human-mediated transmission. Our findings provide new insights into the evolution and dispersal of PDCoV that contribute to our understanding of the critical factors involved in CoVs emergence.

1. Zhao J, Dellicour S, Yan Z, Veit M, Gill MS, He WT, Zhai X, Ji X, Suchard MA, Lemey P, Su S. Early Genomic Surveillance and Phylogeographic Analysis of Getah Virus, a Reemerging Arbovirus, in Livestock in China. J Virol. 2023 Jan 31;97(1):e0109122. doi: 10.1128/jvi.01091-22. Epub 2022 Dec 8. PMID: 36475767; PMCID: PMC9888209. (IF_5year=5.780)

2. He WT#, Hou X#, Zhao J#, et al. Virome characterization of game animals in China reveals a spectrum of emerging pathogens. Cell. 2022 Mar 31;185(7):1117-1129.e8. doi: 10.1016/j.cell.2022.02.014. Epub 2022 Feb 16. PMID: 35298912. (IF_5year=59.901)

3. He WT#, Bollen N#, Xu Y#, et al. Phylogeography Reveals Association between Swine Trade and the Spread of Porcine Epidemic Diarrhea Virus in China and across the World. Mol Biol Evol. 2022 Feb 3;39(2):msab364. doi: 10.1093/molbev/msab364. PMID: 34951645; PMCID: PMC8826572. (IF_5year=20.074)

4. He WT#, Ji X#, He W#, et al. Genomic Epidemiology, Evolution, and Transmission Dynamics of Porcine Deltacoronavirus. Mol Biol Evol. 2020 Sep 1;37(9):2641-2654. doi: 10.1093/molbev/msaa117. PMID: 32407507; PMCID: PMC7454817. (IF_5year=20.074)

5. Sun J#, He WT#, Wang L, et al. COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives. Trends Mol Med. 2020 May;26(5):483-495. doi: 10.1016/j.molmed.2020.02.008. Epub 2020 Mar 21. PMID: 32359479; PMCID: PMC7118693. (IF_5year= 15.638)

6. He WT, Wang L, Zhao Y, Wang N, Li G, Veit M, Bi Y, Gao GF, Su S. Adaption and parallel evolution of human-isolated H5 avian influenza viruses. J Infect. 2020 Jun;80(6):630-638. doi: 10.1016/j.jinf.2020.01.012. Epub 2020 Jan 31. PMID: 32007525.(IF_5year=19.923)

7. He WT, Auclert LZ, Zhai X, Wong G, Zhang C, Zhu H, Xing G, Wang S, He W, Li K, Wang L, Han GZ, Veit M, Zhou J, Su S. Interspecies Transmission, Genetic Diversity, and Evolutionary Dynamics of Pseudorabies Virus. J Infect Dis. 2019 May 5;219(11):1705-1715. doi: 10.1093/infdis/jiy731. PMID: 30590733.(IF_5year = 6.498)

8. Li G, He WT, Zhu H, Bi Y, Wang R, Xing G, Zhang C, Zhou J, Yuen KY, Gao GF, Su S. Origin, Genetic Diversity, and Evolutionary Dynamics of Novel Porcine Circovirus 3. Adv Sci (Weinh). 2018 Jul 4;5(9):1800275. doi: 10.1002/advs.201800275. PMID: 30250786; PMCID: PMC6145280.(IF_5year = 18.939)

Jianjun Dai

Wan-Ting He

Yanmin Ju