tetano
Editor, Senior Moderator
Nat Commun
. 2024 Oct 8;15(1):8708.
doi: 10.1038/s41467-024-52818-0. Coronavirus envelope protein activates TMED10-mediated unconventional secretion of inflammatory factors
Lei Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Lijingyao Zhang[SUP] #[/SUP][SUP] 1 3 [/SUP], Xinyan Hao[SUP] 1 2 [/SUP], Yang Wang[SUP] 1 3 [/SUP], Xiaochun Zhang[SUP] 2 [/SUP], Liang Ge[SUP] 1 3 [/SUP], Peihui Wang[SUP] 4 [/SUP], Boxue Tian[SUP] 2 [/SUP], Min Zhang[SUP] 5 6 [/SUP]
Affiliations
The precise cellular mechanisms underlying heightened proinflammatory cytokine production during coronavirus infection remain incompletely understood. Here we identify the envelope (E) protein in severe coronaviruses (SARS-CoV-2, SARS, or MERS) as a potent inducer of interleukin-1 release, intensifying lung inflammation through the activation of TMED10-mediated unconventional protein secretion (UcPS). In contrast, the E protein of mild coronaviruses (229E, HKU1, or OC43) demonstrates a less pronounced effect. The E protein of severe coronaviruses contains an SS/DS motif, which is not present in milder strains and facilitates interaction with TMED10. This interaction enhances TMED10-oligomerization, facilitating UcPS cargo translocation into the ER-Golgi intermediate compartment (ERGIC)-a pivotal step in interleukin-1 UcPS. Progesterone analogues were identified as compounds inhibiting E-enhanced release of proinflammatory factors and lung inflammation in a Mouse Hepatitis Virus (MHV) infection model. These findings elucidate a molecular mechanism driving coronavirus-induced hyperinflammation, proposing the E-TMED10 interaction as a potential therapeutic target to counteract the adverse effects of coronavirus-induced inflammation.
. 2024 Oct 8;15(1):8708.
doi: 10.1038/s41467-024-52818-0. Coronavirus envelope protein activates TMED10-mediated unconventional secretion of inflammatory factors
Lei Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Lijingyao Zhang[SUP] #[/SUP][SUP] 1 3 [/SUP], Xinyan Hao[SUP] 1 2 [/SUP], Yang Wang[SUP] 1 3 [/SUP], Xiaochun Zhang[SUP] 2 [/SUP], Liang Ge[SUP] 1 3 [/SUP], Peihui Wang[SUP] 4 [/SUP], Boxue Tian[SUP] 2 [/SUP], Min Zhang[SUP] 5 6 [/SUP]
Affiliations
- PMID: 39379362
- PMCID: PMC11461611
- DOI: 10.1038/s41467-024-52818-0
The precise cellular mechanisms underlying heightened proinflammatory cytokine production during coronavirus infection remain incompletely understood. Here we identify the envelope (E) protein in severe coronaviruses (SARS-CoV-2, SARS, or MERS) as a potent inducer of interleukin-1 release, intensifying lung inflammation through the activation of TMED10-mediated unconventional protein secretion (UcPS). In contrast, the E protein of mild coronaviruses (229E, HKU1, or OC43) demonstrates a less pronounced effect. The E protein of severe coronaviruses contains an SS/DS motif, which is not present in milder strains and facilitates interaction with TMED10. This interaction enhances TMED10-oligomerization, facilitating UcPS cargo translocation into the ER-Golgi intermediate compartment (ERGIC)-a pivotal step in interleukin-1 UcPS. Progesterone analogues were identified as compounds inhibiting E-enhanced release of proinflammatory factors and lung inflammation in a Mouse Hepatitis Virus (MHV) infection model. These findings elucidate a molecular mechanism driving coronavirus-induced hyperinflammation, proposing the E-TMED10 interaction as a potential therapeutic target to counteract the adverse effects of coronavirus-induced inflammation.