tetano
Editor, Senior Moderator
J Virol
. 2024 Sep 17:e0107224.
doi: 10.1128/jvi.01072-24. Online ahead of print. Palmitoylation of SARS-CoV-2 Envelope protein is central to virus particle formation
Zhaohuan Wang[SUP] #[/SUP][SUP] 1 [/SUP], Manman Qiu[SUP] #[/SUP][SUP] 1 [/SUP], Yue Ji[SUP] 1 [/SUP], Keli Chai[SUP] 1 [/SUP], Chenxi Liu[SUP] 1 [/SUP], Fengwen Xu[SUP] 2 [/SUP], Fei Guo[SUP] 2 [/SUP], Juan Tan[SUP] 1 [/SUP], Ruikang Liu[SUP] 1 3 [/SUP], Wentao Qiao[SUP] 1 [/SUP]
Affiliations
The Envelope (E) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an integral structural protein in the virus particles. However, its role in the assembly of virions and the underlying molecular mechanisms are yet to be elucidated, including whether the function of E protein is regulated by post-translational modifications. In the present study, we report that SARS-CoV-2 E protein is palmitoylated at C40, C43, and C44 by palmitoyltransferases zDHHC3, 6, 12, 15, and 20. Mutating these three cysteines to serines (C40/43/44S) reduced the stability of E protein, decreased the interaction of E with structural proteins Spike, Membrane, and Nucleocapsid, and thereby inhibited the production of virus-like particles (VLPs) and VLP-mediated luciferase transcriptional delivery. Specifically, the C40/43/44S mutation of E protein reduced the density of VLPs. Collectively, these results demonstrate that palmitoylation of E protein is vital for its function in the assembly of SARS-CoV-2 particles.IMPORTANCEIn this study, we systematically examined the biochemistry of palmitoylation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) E protein and demonstrated that palmitoylation of SARS-CoV-2 E protein is required for virus-like particle (VLP) production and maintaining normal particle density. These results suggest that palmitoylated E protein is central for proper morphogenesis of SARS-CoV-2 VLPs in densities required for viral infectivity. This study presents a significant advancement in the understanding of how palmitoylation of viral proteins is vital for assembling SARS-CoV-2 particles and supports that palmitoyl acyltransferases can be potential therapeutic targets for the development of SARS-CoV-2 inhibitors.
Keywords: Envelope protein; SARS-CoV-2; palmitoylation; virus-like particles.
. 2024 Sep 17:e0107224.
doi: 10.1128/jvi.01072-24. Online ahead of print. Palmitoylation of SARS-CoV-2 Envelope protein is central to virus particle formation
Zhaohuan Wang[SUP] #[/SUP][SUP] 1 [/SUP], Manman Qiu[SUP] #[/SUP][SUP] 1 [/SUP], Yue Ji[SUP] 1 [/SUP], Keli Chai[SUP] 1 [/SUP], Chenxi Liu[SUP] 1 [/SUP], Fengwen Xu[SUP] 2 [/SUP], Fei Guo[SUP] 2 [/SUP], Juan Tan[SUP] 1 [/SUP], Ruikang Liu[SUP] 1 3 [/SUP], Wentao Qiao[SUP] 1 [/SUP]
Affiliations
- PMID: 39287388
- DOI: 10.1128/jvi.01072-24
The Envelope (E) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an integral structural protein in the virus particles. However, its role in the assembly of virions and the underlying molecular mechanisms are yet to be elucidated, including whether the function of E protein is regulated by post-translational modifications. In the present study, we report that SARS-CoV-2 E protein is palmitoylated at C40, C43, and C44 by palmitoyltransferases zDHHC3, 6, 12, 15, and 20. Mutating these three cysteines to serines (C40/43/44S) reduced the stability of E protein, decreased the interaction of E with structural proteins Spike, Membrane, and Nucleocapsid, and thereby inhibited the production of virus-like particles (VLPs) and VLP-mediated luciferase transcriptional delivery. Specifically, the C40/43/44S mutation of E protein reduced the density of VLPs. Collectively, these results demonstrate that palmitoylation of E protein is vital for its function in the assembly of SARS-CoV-2 particles.IMPORTANCEIn this study, we systematically examined the biochemistry of palmitoylation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) E protein and demonstrated that palmitoylation of SARS-CoV-2 E protein is required for virus-like particle (VLP) production and maintaining normal particle density. These results suggest that palmitoylated E protein is central for proper morphogenesis of SARS-CoV-2 VLPs in densities required for viral infectivity. This study presents a significant advancement in the understanding of how palmitoylation of viral proteins is vital for assembling SARS-CoV-2 particles and supports that palmitoyl acyltransferases can be potential therapeutic targets for the development of SARS-CoV-2 inhibitors.
Keywords: Envelope protein; SARS-CoV-2; palmitoylation; virus-like particles.