학술논문
ACE2-independent infection of T lymphocytes by SARS-CoV-2
Document Type
article
Author
Xu-Rui Shen; Rong Geng; Qian Li; Ying Chen; Shu-Fen Li; Qi Wang; Juan Min; Yong Yang; Bei Li; Ren-Di Jiang; Xi Wang; Xiao-Shuang Zheng; Yan Zhu; Jing-Kun Jia; Xing-Lou Yang; Mei-Qin Liu; Qian-Chun Gong; Yu-Lan Zhang; Zhen-Qiong Guan; Hui-Ling Li; Zhen-Hua Zheng; Zheng-Li Shi; Hui-Lan Zhang; Ke Peng; Peng Zhou
Source
Signal Transduction and Targeted Therapy, Vol 7, Iss 1, Pp 1-11 (2022)
Subject
Language
English
ISSN
2059-3635
Abstract
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.