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Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission.
J Virol. 2019 12 15; 93(24)JV

Abstract

Outbreaks of severe diarrhea in neonatal piglets in Guangdong, China, in 2017 resulted in the isolation and discovery of a novel swine enteric alphacoronavirus (SeACoV) derived from the species Rhinolophus bat coronavirus HKU2 (Y. Pan, X. Tian, P. Qin, B. Wang, et al., Vet Microbiol 211:15-21, 2017). SeACoV was later referred to as swine acute diarrhea syndrome CoV (SADS-CoV) by another group (P. Zhou, H. Fan, T. Lan, X.-L. Yang, et al., Nature 556:255-258, 2018). The present study was set up to investigate the potential species barriers of SADS-CoV in vitro and in vivo We first demonstrated that SADS-CoV possesses a broad species tropism and is able to infect cell lines from diverse species, including bats, mice, rats, gerbils, hamsters, pigs, chickens, nonhuman primates, and humans. Trypsin contributes to but is not essential for SADS-CoV propagation in vitro Furthermore, C57BL/6J mice were inoculated with the virus via oral or intraperitoneal routes. Although the mice exhibited only subclinical infection, they supported viral replication and prolonged infection in the spleen. SADS-CoV nonstructural proteins and double-stranded RNA were detected in splenocytes of the marginal zone on the edge of lymphatic follicles, indicating active replication of SADS-CoV in the mouse model. We identified that splenic dendritic cells (DCs) are the major targets of virus infection by immunofluorescence and flow cytometry approaches. Finally, we demonstrated that SADS-CoV does not utilize known CoV receptors for cellular entry. The ability of SADS-CoV to replicate in various cells lines from a broad range of species and the unexpected tropism for murine DCs provide important insights into the biology of this bat-origin CoV, highlighting its possible ability to cross interspecies barriers.IMPORTANCE Infections with bat-origin coronaviruses (CoVs) (severe acute respiratory syndrome CoV [SARS-CoV] and Middle East respiratory syndrome CoV [MERS-CoV]) have caused severe illness in humans after "host jump" events. Recently, a novel bat-HKU2-like CoV named swine acute diarrhea syndrome CoV (SADS-CoV) has emerged in southern China, causing lethal diarrhea in newborn piglets. It is important to assess the species barriers of SADS-CoV infection since the animal hosts (other than pigs and bats) and zoonotic potential are still unknown. An in vitro susceptibility study revealed a broad species tropism of SADS-CoV, including various rodent and human cell lines. We established a mouse model of SADS-CoV infection, identifying its active replication in splenic dendritic cells, which suggests that SADS-CoV has the potential to infect rodents. These findings highlight the potential cross-species transmissibility of SADS-CoV, although further surveillance in other animal populations is needed to fully understand the ecology of this bat-HKU2-origin CoV.

Authors+Show Affiliations

Key Laboratory of Animal Virology of Ministry of Agriculture, Institute of Preventive Veterinary Medicine, Department of Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Key Laboratory of Animal Virology of Ministry of Agriculture, Institute of Preventive Veterinary Medicine, Department of Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Key Laboratory of Animal Virology of Ministry of Agriculture, Institute of Preventive Veterinary Medicine, Department of Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Key Laboratory of Animal Virology of Ministry of Agriculture, Institute of Preventive Veterinary Medicine, Department of Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Key Laboratory of Animal Virology of Ministry of Agriculture, Institute of Preventive Veterinary Medicine, Department of Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Key Laboratory of Animal Virology of Ministry of Agriculture, Institute of Preventive Veterinary Medicine, Department of Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Key Laboratory of Animal Virology of Ministry of Agriculture, Institute of Preventive Veterinary Medicine, Department of Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Key Laboratory of Animal Virology of Ministry of Agriculture, Institute of Preventive Veterinary Medicine, Department of Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang, China shuzhu@zju.edu.cn yhuang@zju.edu.cn.Key Laboratory of Animal Virology of Ministry of Agriculture, Institute of Preventive Veterinary Medicine, Department of Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang, China shuzhu@zju.edu.cn yhuang@zju.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31554686

Citation

Yang, Yong-Le, et al. "Broad Cross-Species Infection of Cultured Cells By Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells in Vivo Highlight Its Potential for Diverse Interspecies Transmission." Journal of Virology, vol. 93, no. 24, 2019.
Yang YL, Qin P, Wang B, et al. Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission. J Virol. 2019;93(24).
Yang, Y. L., Qin, P., Wang, B., Liu, Y., Xu, G. H., Peng, L., Zhou, J., Zhu, S. J., & Huang, Y. W. (2019). Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission. Journal of Virology, 93(24). https://doi.org/10.1128/JVI.01448-19
Yang YL, et al. Broad Cross-Species Infection of Cultured Cells By Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells in Vivo Highlight Its Potential for Diverse Interspecies Transmission. J Virol. 2019 12 15;93(24) PubMed PMID: 31554686.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission. AU - Yang,Yong-Le, AU - Qin,Pan, AU - Wang,Bin, AU - Liu,Yan, AU - Xu,Guo-Han, AU - Peng,Lei, AU - Zhou,Jiyong, AU - Zhu,Shu Jeffrey, AU - Huang,Yao-Wei, Y1 - 2019/11/26/ PY - 2019/08/27/received PY - 2019/09/19/accepted PY - 2019/9/27/pubmed PY - 2020/6/5/medline PY - 2019/9/27/entrez KW - Coronavirus KW - SADS-CoV KW - interspecies transmission KW - mouse infection model JF - Journal of virology JO - J Virol VL - 93 IS - 24 N2 - Outbreaks of severe diarrhea in neonatal piglets in Guangdong, China, in 2017 resulted in the isolation and discovery of a novel swine enteric alphacoronavirus (SeACoV) derived from the species Rhinolophus bat coronavirus HKU2 (Y. Pan, X. Tian, P. Qin, B. Wang, et al., Vet Microbiol 211:15-21, 2017). SeACoV was later referred to as swine acute diarrhea syndrome CoV (SADS-CoV) by another group (P. Zhou, H. Fan, T. Lan, X.-L. Yang, et al., Nature 556:255-258, 2018). The present study was set up to investigate the potential species barriers of SADS-CoV in vitro and in vivo We first demonstrated that SADS-CoV possesses a broad species tropism and is able to infect cell lines from diverse species, including bats, mice, rats, gerbils, hamsters, pigs, chickens, nonhuman primates, and humans. Trypsin contributes to but is not essential for SADS-CoV propagation in vitro Furthermore, C57BL/6J mice were inoculated with the virus via oral or intraperitoneal routes. Although the mice exhibited only subclinical infection, they supported viral replication and prolonged infection in the spleen. SADS-CoV nonstructural proteins and double-stranded RNA were detected in splenocytes of the marginal zone on the edge of lymphatic follicles, indicating active replication of SADS-CoV in the mouse model. We identified that splenic dendritic cells (DCs) are the major targets of virus infection by immunofluorescence and flow cytometry approaches. Finally, we demonstrated that SADS-CoV does not utilize known CoV receptors for cellular entry. The ability of SADS-CoV to replicate in various cells lines from a broad range of species and the unexpected tropism for murine DCs provide important insights into the biology of this bat-origin CoV, highlighting its possible ability to cross interspecies barriers.IMPORTANCE Infections with bat-origin coronaviruses (CoVs) (severe acute respiratory syndrome CoV [SARS-CoV] and Middle East respiratory syndrome CoV [MERS-CoV]) have caused severe illness in humans after "host jump" events. Recently, a novel bat-HKU2-like CoV named swine acute diarrhea syndrome CoV (SADS-CoV) has emerged in southern China, causing lethal diarrhea in newborn piglets. It is important to assess the species barriers of SADS-CoV infection since the animal hosts (other than pigs and bats) and zoonotic potential are still unknown. An in vitro susceptibility study revealed a broad species tropism of SADS-CoV, including various rodent and human cell lines. We established a mouse model of SADS-CoV infection, identifying its active replication in splenic dendritic cells, which suggests that SADS-CoV has the potential to infect rodents. These findings highlight the potential cross-species transmissibility of SADS-CoV, although further surveillance in other animal populations is needed to fully understand the ecology of this bat-HKU2-origin CoV. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/31554686/Broad_Cross_Species_Infection_of_Cultured_Cells_by_Bat_HKU2_Related_Swine_Acute_Diarrhea_Syndrome_Coronavirus_and_Identification_of_Its_Replication_in_Murine_Dendritic_Cells_In_Vivo_Highlight_Its_Potential_for_Diverse_Interspecies_Transmission_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31554686/ DB - PRIME DP - Unbound Medicine ER -