tetano
Editor, Senior Moderator
J Cell Sci
. 2023 Feb 21;jcs.260685.
doi: 10.1242/jcs.260685. Online ahead of print.
SARS-CoV-2 infection alkalinizes the ERGIC and lysosomes through the viroporin activity of the viral envelope protein
Wen-An Wang[SUP] 1 [/SUP], Amado Carreras Sureda[SUP] 1 [/SUP], Nicolas Demaurex[SUP] 1 [/SUP]
Affiliations
Abstract
The coronavirus SARS-CoV-2, the agent of the deadly COVID-19 pandemic, is an enveloped virus propagating within the endocytic and secretory organelles of host mammalian cells. Enveloped viruses modify the ionic homeostasis of organelles to render their intra-luminal milieu permissive for viral entry, replication, and egress. Here, we show that infection of Vero E6 cells with the delta variant of the SARS-CoV-2 alkalinizes the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) as well as lysosomes, mimicking the effect of inhibitors of vacuolar proton ATPases. We further show the envelope protein of SARS-CoV-2 accumulates in the ERGIC when expressed in mammalian cells and selectively dissipates the ERGIC pH. This viroporin is prevented by mutations of Val25 but not Asn15 within the channel pore of E. We conclude that the envelope protein acts as a proton channel in the ERGIC to mitigate the acidity of this intermediate compartment. The altered pH homeostasis of the ERGIC likely contributes to the virus fitness and pathogenicity, making the E channel an attractive drug target for the treatment of COVID-19.
Keywords: COVID-19; Coronavirus; Ion channel; Viroporin; Virus-host interactions.
. 2023 Feb 21;jcs.260685.
doi: 10.1242/jcs.260685. Online ahead of print.
SARS-CoV-2 infection alkalinizes the ERGIC and lysosomes through the viroporin activity of the viral envelope protein
Wen-An Wang[SUP] 1 [/SUP], Amado Carreras Sureda[SUP] 1 [/SUP], Nicolas Demaurex[SUP] 1 [/SUP]
Affiliations
- PMID: 36807531
- DOI: 10.1242/jcs.260685
Abstract
The coronavirus SARS-CoV-2, the agent of the deadly COVID-19 pandemic, is an enveloped virus propagating within the endocytic and secretory organelles of host mammalian cells. Enveloped viruses modify the ionic homeostasis of organelles to render their intra-luminal milieu permissive for viral entry, replication, and egress. Here, we show that infection of Vero E6 cells with the delta variant of the SARS-CoV-2 alkalinizes the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) as well as lysosomes, mimicking the effect of inhibitors of vacuolar proton ATPases. We further show the envelope protein of SARS-CoV-2 accumulates in the ERGIC when expressed in mammalian cells and selectively dissipates the ERGIC pH. This viroporin is prevented by mutations of Val25 but not Asn15 within the channel pore of E. We conclude that the envelope protein acts as a proton channel in the ERGIC to mitigate the acidity of this intermediate compartment. The altered pH homeostasis of the ERGIC likely contributes to the virus fitness and pathogenicity, making the E channel an attractive drug target for the treatment of COVID-19.
Keywords: COVID-19; Coronavirus; Ion channel; Viroporin; Virus-host interactions.