tetano
Editor, Senior Moderator
Cell Mol Life Sci
. 2023 Nov 9;80(12):353.
doi: 10.1007/s00018-023-05008-y. The KxGxYR and DxE motifs in the C-tail of the Middle East respiratory syndrome coronavirus membrane protein are crucial for infectious virus assembly
Lowiese Desmarets[SUP] 1 [/SUP], Adeline Danneels[SUP] 1 [/SUP], Julien Burlaud-Gaillard[SUP] 2 3 [/SUP], Emmanuelle Blanchard[SUP] 2 3 [/SUP], Jean Dubuisson[SUP] 1 [/SUP], Sandrine Belouzard[SUP] 4 [/SUP]
Affiliations
The coronavirus' (CoV) membrane (M) protein is the driving force during assembly, but this process remains poorly characterized. Previously, we described two motifs in the C-tail of the Middle East respiratory syndrome CoV (MERS-CoV) M protein involved in its endoplasmic reticulum (ER) exit ([SUB]211[/SUB]DxE[SUB]213[/SUB]) and trans-Golgi network (TGN) retention ([SUB]199[/SUB]KxGxYR[SUB]204[/SUB]). Here, their function in virus assembly was investigated by two different virus-like particle (VLP) assays and by mutating both motifs in an infectious MERS-CoV cDNA clone. It was shown that the [SUB]199[/SUB]KxGxYR[SUB]204[/SUB] motif was essential for VLP and infectious virus assembly. Moreover, the mislocalization of the M protein induced by mutation of this motif prevented M-E interaction. Hampering the ER export of M by mutating its [SUB]211[/SUB]DxE[SUB]213[/SUB] motif still allowed the formation of nucleocapsid-empty VLPs, but prevented the formation of fully assembled VLPs and infectious particles. Taken together, these data show that the MERS-CoV assembly process highly depends on the correct intracellular trafficking of its M protein, and hence that not only specific protein-protein interacting motifs but also correct subcellular localization of the M protein in infected cells is essential for virus formation and should be taken into consideration when studying the assembly process.
Keywords: Coronavirus; Endoplasmic reticulum exit; Intracellular trafficking; Membrane protein; Trans-Golgi network retention; Viral assembly.
. 2023 Nov 9;80(12):353.
doi: 10.1007/s00018-023-05008-y. The KxGxYR and DxE motifs in the C-tail of the Middle East respiratory syndrome coronavirus membrane protein are crucial for infectious virus assembly
Lowiese Desmarets[SUP] 1 [/SUP], Adeline Danneels[SUP] 1 [/SUP], Julien Burlaud-Gaillard[SUP] 2 3 [/SUP], Emmanuelle Blanchard[SUP] 2 3 [/SUP], Jean Dubuisson[SUP] 1 [/SUP], Sandrine Belouzard[SUP] 4 [/SUP]
Affiliations
- PMID: 37940699
- DOI: 10.1007/s00018-023-05008-y
The coronavirus' (CoV) membrane (M) protein is the driving force during assembly, but this process remains poorly characterized. Previously, we described two motifs in the C-tail of the Middle East respiratory syndrome CoV (MERS-CoV) M protein involved in its endoplasmic reticulum (ER) exit ([SUB]211[/SUB]DxE[SUB]213[/SUB]) and trans-Golgi network (TGN) retention ([SUB]199[/SUB]KxGxYR[SUB]204[/SUB]). Here, their function in virus assembly was investigated by two different virus-like particle (VLP) assays and by mutating both motifs in an infectious MERS-CoV cDNA clone. It was shown that the [SUB]199[/SUB]KxGxYR[SUB]204[/SUB] motif was essential for VLP and infectious virus assembly. Moreover, the mislocalization of the M protein induced by mutation of this motif prevented M-E interaction. Hampering the ER export of M by mutating its [SUB]211[/SUB]DxE[SUB]213[/SUB] motif still allowed the formation of nucleocapsid-empty VLPs, but prevented the formation of fully assembled VLPs and infectious particles. Taken together, these data show that the MERS-CoV assembly process highly depends on the correct intracellular trafficking of its M protein, and hence that not only specific protein-protein interacting motifs but also correct subcellular localization of the M protein in infected cells is essential for virus formation and should be taken into consideration when studying the assembly process.
Keywords: Coronavirus; Endoplasmic reticulum exit; Intracellular trafficking; Membrane protein; Trans-Golgi network retention; Viral assembly.