Increased Pathogenicity and Virulence of Middle East Respiratory Syndrome Coronavirus Clade B In Vitro and In Vivo

Wang, Yanqun1; Sun, Jing1; Li, Xiaobo2; Zhu, Airu1; Guan, Wenda1; Sun, De-Qiang3; Gan, Mian1; Niu, Xuefeng1; Dai, Jun2; Zhang, Lu4; Zhang, Zhaoyong1; Shi, Yongxia2; Huang, Shuxiang2; Mok, Chris Ka Pun5; Yang, Zifeng1; Wang, Zhongfang1; Tan, Wenjie6; Li, Yimin1; Chen, Ling1,7; Chen, Rongchang8; Peiris, Malik1,5; Zhong, Nanshan1; Zhao, Jingxian1; Huang, Jicheng2; Zhao, Jincun1,4

2020-08

10.1128/JVI.00861-20

JOURNAL OF VIROLOGY   影响因子和分区

0022-538X

1098-5514

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory disease in humans. MERS-CoV strains from early epidemic clade A and contemporary epidemic clade B have not been phenotypically characterized to compare their abilities to infect cells and mice. We isolated the clade B MERS-CoV ChinaGD01 strain from a patient infected during the South Korean MERS outbreak in 2015 and compared the phylogenetics and pathogenicity of MERS-CoV EMC/2012 (clade A) and ChinaGD01 (clade B) in vitro and in vivo. Genome alignment analysis showed that most clade-specific mutations occurred in the orf1ab gene, including mutations that were predicted to be potential glycosylation sites. Minor differences in viral growth but no significant differences in plaque size or sensitivity to beta interferon (IFN-beta) were detected between these two viruses in vitro. ChinaGD01 virus infection induced more weight loss and inflammatory cytokine production in human DPP4-transduced mice. Viral titers were higher in the lungs of ChinaGD01-infected mice than with EMC/2012 infection. Decreased virus-specific CD4(+) and CD8(+) T cell numbers were detected in the lungs of ChinaGD01-infected mice. In conclusion, MERS-CoV evolution induced changes to reshape its pathogenicity and virulence in vitro and in vivo and to evade adaptive immune response to hinder viral clearance.

MERS-CoV T cell response pathogenicity phylogenetics virulence

SCI

英语

其他

Guangdong Provincial Department of Science and Technology[2018B020207013] ; National Key Research and Development Program of China[2018YFC1200100][2016YFC1202701] ; National Science and Technology Major Project[2018ZX10301403-001-003][2018ZX10101002] ; National Natural Science Foundation of China[81772191][81702047][91842106][8181101118] ; Thousand Talents Plan Award of China 2015[SKLRD-QN-201715][SKLRD-QN-201912] ; State Key Laboratory of Respiratory Disease[SKLRD-QN-201715][SKLRD-QN-201912] ; Guangzhou Medical University High-level University Innovation Team Training Program (Guangzhou Medical University release [2017])[159] ; National Key Technology RD Program[2018YFC1311900] ; Guangdong Science and Technology Foundation[2019B030316028]

Virology

Virology

WOS:000550175500008

AMER SOC MICROBIOLOGY

MICROBIOLOGY

Web of Science

1.Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Natl Clin Res Ctr Resp Dis, Affiliated Hosp 1,State Key Lab Resp Dis, Guangzhou, Peoples R China
2.Guangzhou Custom, Technol Ctr, Guangzhou, Peoples R China
3.Guangzhou Med Univ, State Key Lab Resp Dis, Affiliated Hosp 5, Guangzhou, Peoples R China
4.Guangzhou Med Univ, Inst Infect Dis, Guangzhou Peoples Hosp 8, Guangzhou, Peoples R China
5.Univ Hong Kong, HKU Li KaShing Fac Med, Sch Publ Hlth, Hong Kong HKU Pasteur Res Pole, Hong Kong, Peoples R China
6.Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, Key Lab Med Virol, Minist Hlth, Beijing, Peoples R China
7.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou, Peoples R China
8.South Univ Sci & Technol China, Affiliated Hosp 5, Shenzhen Inst Resp Dis, Shenzhen Peoples Hosp, Shenzhen, Peoples R China

Wang, Yanqun,Sun, Jing,Li, Xiaobo,et al. Increased Pathogenicity and Virulence of Middle East Respiratory Syndrome Coronavirus Clade B In Vitro and In Vivo[J]. JOURNAL OF VIROLOGY,2020,94(15).

Wang, Yanqun.,Sun, Jing.,Li, Xiaobo.,Zhu, Airu.,Guan, Wenda.,...&Zhao, Jincun.(2020).Increased Pathogenicity and Virulence of Middle East Respiratory Syndrome Coronavirus Clade B In Vitro and In Vivo.JOURNAL OF VIROLOGY,94(15).

Wang, Yanqun,et al."Increased Pathogenicity and Virulence of Middle East Respiratory Syndrome Coronavirus Clade B In Vitro and In Vivo".JOURNAL OF VIROLOGY 94.15(2020).