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ACE2-independent infection of T lymphocytes by SARS-CoV-2.
Shen, Xu-Rui; Geng, Rong; Li, Qian; Chen, Ying; Li, Shu-Fen; Wang, Qi; Min, Juan; Yang, Yong; Li, Bei; Jiang, Ren-Di; Wang, Xi; Zheng, Xiao-Shuang; Zhu, Yan; Jia, Jing-Kun; Yang, Xing-Lou; Liu, Mei-Qin; Gong, Qian-Chun; Zhang, Yu-Lan; Guan, Zhen-Qiong; Li, Hui-Ling; Zheng, Zhen-Hua; Shi, Zheng-Li; Zhang, Hui-Lan; Peng, Ke; Zhou, Peng.
  • Shen XR; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Geng R; University of Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Li Q; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Chen Y; University of Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Li SF; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Wang Q; University of Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Min J; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Yang Y; University of Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Li B; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Jiang RD; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Wang X; University of Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Zheng XS; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Zhu Y; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Jia JK; University of Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Yang XL; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Liu MQ; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Gong QC; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Zhang YL; University of Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Guan ZQ; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Li HL; University of Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Zheng ZH; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Shi ZL; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Zhang HL; University of Chinese Academy of Sciences, Beijing, People's Republic of China.
  • Peng K; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
  • Zhou P; CAS Key Laboratory of Special Pathogens & State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
Signal Transduct Target Ther ; 7(1): 83, 2022 03 11.
Article in English | MEDLINE | ID: covidwho-1740428
ABSTRACT
SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: T-Lymphocytes / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Journal: Signal Transduct Target Ther Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: T-Lymphocytes / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Journal: Signal Transduct Target Ther Year: 2022 Document Type: Article