tetano
Editor, Senior Moderator
Int J Med Microbiol
. 2025 Sep 2:320:151671.
doi: 10.1016/j.ijmm.2025.151671. Online ahead of print. SARS-CoV-2 nucleocapsid protein delays cell cycle in S-phase
Jinming Liu[SUP] 1 [/SUP], Mengyu Liu[SUP] 2 [/SUP], Xiaoyan Yu[SUP] 2 [/SUP], Pei-Hui Wang[SUP] 3 [/SUP], Xue Guan[SUP] 4 [/SUP], Wenbo Huo[SUP] 2 [/SUP], Jing Zhang[SUP] 3 [/SUP], Minna Cui[SUP] 2 [/SUP], Xinhua Li[SUP] 2 [/SUP], Xinhe Zhou[SUP] 2 [/SUP], Siyu Liu[SUP] 2 [/SUP], Cong Wang[SUP] 2 [/SUP], Changrui Huang[SUP] 2 [/SUP], Jinghua Yu[SUP] 5 [/SUP]
Affiliations
The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as the causative agent of COVID-19 precipitated a global health crisis of unprecedented scale. SARS-CoV-2 has been shown to interfere specifically with S phase progression during early stages of infection. Nucleocapsid (N) is an important structural protein. The abundance and early presence of N suggest that the N protein may play a pivotal role in determining the fate of host cells post-infection, including in cell cycle regulation. Our observations reveal that the SARS-CoV-2 N protein actually induces S phase arrest by promoting S phase entry and simultaneously blocking exit from this phase, which is different from previous report G1/S blockage, others describe G1 and G2/M arrest. Prolonged cell cycle arrest is frequently linked to cell death, while our data suggests the N protein curtails cell proliferation, slowing down cell growth without actively triggering cell death. Intriguingly, removing the N-arm, SR-rich region, CTD, or C-tail each abolishes the N protein's ability to suppress cell growth, whereas deletion of the NTD does not impact this capability, nor does it affect S phase arrest. All told, the SARS-CoV-2 N protein emerges as a multifunctional actor, not only driving key aspects of viral replication but also exerting significant effects on host cell physiology by modulating cell cycle progression and growth.
Keywords: Cell cycle arrest; Cell growth; Nucleocapsid protein; SARS-CoV-2.
. 2025 Sep 2:320:151671.
doi: 10.1016/j.ijmm.2025.151671. Online ahead of print. SARS-CoV-2 nucleocapsid protein delays cell cycle in S-phase
Jinming Liu[SUP] 1 [/SUP], Mengyu Liu[SUP] 2 [/SUP], Xiaoyan Yu[SUP] 2 [/SUP], Pei-Hui Wang[SUP] 3 [/SUP], Xue Guan[SUP] 4 [/SUP], Wenbo Huo[SUP] 2 [/SUP], Jing Zhang[SUP] 3 [/SUP], Minna Cui[SUP] 2 [/SUP], Xinhua Li[SUP] 2 [/SUP], Xinhe Zhou[SUP] 2 [/SUP], Siyu Liu[SUP] 2 [/SUP], Cong Wang[SUP] 2 [/SUP], Changrui Huang[SUP] 2 [/SUP], Jinghua Yu[SUP] 5 [/SUP]
Affiliations
- PMID: 40912153
- DOI: 10.1016/j.ijmm.2025.151671
The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as the causative agent of COVID-19 precipitated a global health crisis of unprecedented scale. SARS-CoV-2 has been shown to interfere specifically with S phase progression during early stages of infection. Nucleocapsid (N) is an important structural protein. The abundance and early presence of N suggest that the N protein may play a pivotal role in determining the fate of host cells post-infection, including in cell cycle regulation. Our observations reveal that the SARS-CoV-2 N protein actually induces S phase arrest by promoting S phase entry and simultaneously blocking exit from this phase, which is different from previous report G1/S blockage, others describe G1 and G2/M arrest. Prolonged cell cycle arrest is frequently linked to cell death, while our data suggests the N protein curtails cell proliferation, slowing down cell growth without actively triggering cell death. Intriguingly, removing the N-arm, SR-rich region, CTD, or C-tail each abolishes the N protein's ability to suppress cell growth, whereas deletion of the NTD does not impact this capability, nor does it affect S phase arrest. All told, the SARS-CoV-2 N protein emerges as a multifunctional actor, not only driving key aspects of viral replication but also exerting significant effects on host cell physiology by modulating cell cycle progression and growth.
Keywords: Cell cycle arrest; Cell growth; Nucleocapsid protein; SARS-CoV-2.