tetano
Editor, Senior Moderator
J Biol Chem
. 2022 Sep 19;298(11):102511.
doi: 10.1016/j.jbc.2022.102511. Online ahead of print.
SARS-CoV-2 hijacks macropinocytosis to facilitate its entry and promote viral spike-mediated cell-to-cell fusion
Yu-Yuan Zhang[SUP] 1 [/SUP], Ronghui Liang[SUP] 2 [/SUP], Shu-Jie Wang[SUP] 1 [/SUP], Zi-Wei Ye[SUP] 2 [/SUP], Tong-Yun Wang[SUP] 1 [/SUP], Meng Chen[SUP] 1 [/SUP], Jianbo Liu[SUP] 1 [/SUP], Lei Na[SUP] 1 [/SUP], Yue-Lin Yang[SUP] 1 [/SUP], Yong-Bo Yang[SUP] 1 [/SUP], Shuofeng Yuan[SUP] 3 [/SUP], Xin Yin[SUP] 4 [/SUP], Xue-Hui Cai[SUP] 1 [/SUP], Yan-Dong Tang[SUP] 5 [/SUP]
Affiliations
Abstract
Revealing the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and cell-to-cell spread might provide insights for understanding the underlying mechanisms of viral pathogenesis, tropism, and virulence. The signaling pathways involved in SARS-CoV-2 entry and viral spike-mediated cell-to-cell fusion remain elusive. In the current study, we found that macropinocytosis inhibitors significantly suppressed SARS-CoV-2 infection at both the entry and viral spike-mediated cell-to-cell fusion steps. We demonstrated that SARS-CoV-2 entry required the small GTPase Rac1 and its effector kinase p21-activated kinase 1 by dominant-negative and RNAi assays in human embryonic kidney 293T-angiotensin-converting enzyme 2 cells and that the serine protease transmembrane serine protease 2 reversed the decrease in SARS-CoV-2 entry caused by the macropinocytosis inhibitors. Moreover, in the cell-to-cell fusion assay, we confirmed that macropinocytosis inhibitors significantly decreased viral spike-mediated cell-to-cell fusion. Overall, we provided evidence that SARS-CoV-2 utilizes a macropinocytosis pathway to enter target cells and to efficiently promote viral spike-mediated cell-to-cell fusion.
Keywords: SARS-CoV-2; cell-to-cell; entry; fusion; macropinocytosis.
. 2022 Sep 19;298(11):102511.
doi: 10.1016/j.jbc.2022.102511. Online ahead of print.
SARS-CoV-2 hijacks macropinocytosis to facilitate its entry and promote viral spike-mediated cell-to-cell fusion
Yu-Yuan Zhang[SUP] 1 [/SUP], Ronghui Liang[SUP] 2 [/SUP], Shu-Jie Wang[SUP] 1 [/SUP], Zi-Wei Ye[SUP] 2 [/SUP], Tong-Yun Wang[SUP] 1 [/SUP], Meng Chen[SUP] 1 [/SUP], Jianbo Liu[SUP] 1 [/SUP], Lei Na[SUP] 1 [/SUP], Yue-Lin Yang[SUP] 1 [/SUP], Yong-Bo Yang[SUP] 1 [/SUP], Shuofeng Yuan[SUP] 3 [/SUP], Xin Yin[SUP] 4 [/SUP], Xue-Hui Cai[SUP] 1 [/SUP], Yan-Dong Tang[SUP] 5 [/SUP]
Affiliations
- PMID: 36259516
- DOI: 10.1016/j.jbc.2022.102511
Abstract
Revealing the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and cell-to-cell spread might provide insights for understanding the underlying mechanisms of viral pathogenesis, tropism, and virulence. The signaling pathways involved in SARS-CoV-2 entry and viral spike-mediated cell-to-cell fusion remain elusive. In the current study, we found that macropinocytosis inhibitors significantly suppressed SARS-CoV-2 infection at both the entry and viral spike-mediated cell-to-cell fusion steps. We demonstrated that SARS-CoV-2 entry required the small GTPase Rac1 and its effector kinase p21-activated kinase 1 by dominant-negative and RNAi assays in human embryonic kidney 293T-angiotensin-converting enzyme 2 cells and that the serine protease transmembrane serine protease 2 reversed the decrease in SARS-CoV-2 entry caused by the macropinocytosis inhibitors. Moreover, in the cell-to-cell fusion assay, we confirmed that macropinocytosis inhibitors significantly decreased viral spike-mediated cell-to-cell fusion. Overall, we provided evidence that SARS-CoV-2 utilizes a macropinocytosis pathway to enter target cells and to efficiently promote viral spike-mediated cell-to-cell fusion.
Keywords: SARS-CoV-2; cell-to-cell; entry; fusion; macropinocytosis.