Role of SARS‑CoV‑2 nucleocapsid protein in affecting immune cells and insights on its molecular mechanisms

Yan Lu; Ziyu Ye; Xinlan Liu; Liqian Zhou; Xiang Ding; Yiling Hou

doi:10.3892/etm.2023.12203

Role of SARS‑CoV‑2 nucleocapsid protein in affecting immune cells and insights on its molecular mechanisms

Exp Ther Med. 2023 Sep 12;26(5):504. doi: 10.3892/etm.2023.12203. eCollection 2023 Nov.

Authors

Yan Lu¹, Ziyu Ye¹, Xinlan Liu², Liqian Zhou¹, Xiang Ding², Yiling Hou¹

Affiliations

¹ Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), College of Life Sciences, China West Normal University, Nanchong, Sichuan 637009, P.R. China.
² Key Laboratory of Nanchong City of Ecological Environment Protection and Pollution Prevention in Jialing River Basin, College of Environmental Science and Engineering, China West Normal University, Nanchong, Sichuan 637009, P.R. China.

Abstract

The present study aimed to explore the immune regulatory function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein and related mechanisms. In a series of protein activity experiments, SARS-CoV-2 N protein promoted proliferation of three immune cell lines: mouse Raw264.7, human Jurkat and human Raji in a dose-dependent manner. A total of 10 µg/ml N protein could significantly change cell cycle progression of the aforementioned three immune cell lines and could promote quick entry of Raw264.7 cells into G₂/M phase from S phase to achieve rapid growth. Additionally, the N protein could also stimulate Raw264.7 cells to secrete a number of proinflammatory factors such as TNF-α, IL-6 and IL-10. RNA sequencing analysis indicated that the N protein changed the expression of certain genes involved in immune-related functions and four important signaling pathways, including JAK-STAT, TNF, NF-κB and MAPK signaling pathways, which suggested that the N protein may not only regulate the expression of genes involved in the process of resisting viral infection in macrophages of the immune system, but also change cellular signal processing.

Keywords: cell cycle; differently expressed genes; immune cells; severe acute respiratory syndrome coronavirus 2 nucleocapsid; signaling pathway.

Grants and funding

Funding: The present study was supported by The Sichuan Province Science and Technology Support Project (grant nos. 2022NSFSC0107, 2022NZZJ0003 and 22ZYZFSF0009), The Nanchong City Science and Technology Project (grant nos. 20YFZJ0053 and 20YFZJ0054), and The Open Project of Sichuan Provincial Key Laboratory of Central Nervous System Drugs (grant no. 210023-01SZ).