tetano
Editor, Senior Moderator
Sci Adv
. 2021 Aug 18;7(34):eabf8609.
doi: 10.1126/sciadv.abf8609. Print 2021 Aug.
Age-dependent regulation of SARS-CoV-2 cell entry genes and cell death programs correlates with COVID-19 severity
Zintis Inde[SUP] 1 2 [/SUP], Ben A Croker[SUP] 3 [/SUP], Clarence Yapp[SUP] 2 4 [/SUP], Gaurav N Joshi[SUP] 1 2 5 [/SUP], Johan Spetz[SUP] 1 2 [/SUP], Cameron Fraser[SUP] 1 2 [/SUP], Xingping Qin[SUP] 1 2 [/SUP], Le Xu[SUP] 6 [/SUP], Brian Deskin[SUP] 1 [/SUP], Elisa Ghelfi[SUP] 1 [/SUP], Gabrielle Webb[SUP] 1 [/SUP], Aaron F Carlin[SUP] 6 [/SUP], Yanfang Peipei Zhu[SUP] 3 [/SUP], Sandra L Leibel[SUP] 3 7 8 [/SUP], Aaron F Garretson[SUP] 6 [/SUP], Alex E Clark[SUP] 6 [/SUP], Jason M Duran[SUP] 6 [/SUP], Victor Pretorius[SUP] 9 [/SUP], Laura E Crotty-Alexander[SUP] 6 [/SUP], Chendi Li[SUP] 10 [/SUP], Jamie Casey Lee[SUP] 3 [/SUP], Chhinder Sodhi[SUP] 11 [/SUP], David J Hackam[SUP] 11 [/SUP], Xin Sun[SUP] 3 [/SUP], Aaron N Hata[SUP] 10 12 [/SUP], Lester Kobzik[SUP] 1 [/SUP], Jeffrey Miller[SUP] 1 [/SUP], Jin-Ah Park[SUP] 1 [/SUP], Douglas Brownfield[SUP] 1 [/SUP], Hongpeng Jia[SUP] 11 [/SUP], Kristopher A Sarosiek[SUP] 13 2 [/SUP]
Affiliations
Abstract
Novel coronavirus disease 2019 (COVID-19) severity is highly variable, with pediatric patients typically experiencing less severe infection than adults and especially the elderly. The basis for this difference is unclear. We find that mRNA and protein expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, increases with advancing age in distal lung epithelial cells. However, in humans, ACE2 expression exhibits high levels of intra- and interindividual heterogeneity. Further, cells infected with SARS-CoV-2 experience endoplasmic reticulum stress, triggering an unfolded protein response and caspase-mediated apoptosis, a natural host defense system that halts virion production. Apoptosis of infected cells can be selectively induced by treatment with apoptosis-modulating BH3 mimetic drugs. Notably, epithelial cells within young lungs and airways are more primed to undergo apoptosis than those in adults, which may naturally hinder virion production and support milder COVID-19 severity.
. 2021 Aug 18;7(34):eabf8609.
doi: 10.1126/sciadv.abf8609. Print 2021 Aug.
Age-dependent regulation of SARS-CoV-2 cell entry genes and cell death programs correlates with COVID-19 severity
Zintis Inde[SUP] 1 2 [/SUP], Ben A Croker[SUP] 3 [/SUP], Clarence Yapp[SUP] 2 4 [/SUP], Gaurav N Joshi[SUP] 1 2 5 [/SUP], Johan Spetz[SUP] 1 2 [/SUP], Cameron Fraser[SUP] 1 2 [/SUP], Xingping Qin[SUP] 1 2 [/SUP], Le Xu[SUP] 6 [/SUP], Brian Deskin[SUP] 1 [/SUP], Elisa Ghelfi[SUP] 1 [/SUP], Gabrielle Webb[SUP] 1 [/SUP], Aaron F Carlin[SUP] 6 [/SUP], Yanfang Peipei Zhu[SUP] 3 [/SUP], Sandra L Leibel[SUP] 3 7 8 [/SUP], Aaron F Garretson[SUP] 6 [/SUP], Alex E Clark[SUP] 6 [/SUP], Jason M Duran[SUP] 6 [/SUP], Victor Pretorius[SUP] 9 [/SUP], Laura E Crotty-Alexander[SUP] 6 [/SUP], Chendi Li[SUP] 10 [/SUP], Jamie Casey Lee[SUP] 3 [/SUP], Chhinder Sodhi[SUP] 11 [/SUP], David J Hackam[SUP] 11 [/SUP], Xin Sun[SUP] 3 [/SUP], Aaron N Hata[SUP] 10 12 [/SUP], Lester Kobzik[SUP] 1 [/SUP], Jeffrey Miller[SUP] 1 [/SUP], Jin-Ah Park[SUP] 1 [/SUP], Douglas Brownfield[SUP] 1 [/SUP], Hongpeng Jia[SUP] 11 [/SUP], Kristopher A Sarosiek[SUP] 13 2 [/SUP]
Affiliations
- PMID: 34407940
- DOI: 10.1126/sciadv.abf8609
Abstract
Novel coronavirus disease 2019 (COVID-19) severity is highly variable, with pediatric patients typically experiencing less severe infection than adults and especially the elderly. The basis for this difference is unclear. We find that mRNA and protein expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, increases with advancing age in distal lung epithelial cells. However, in humans, ACE2 expression exhibits high levels of intra- and interindividual heterogeneity. Further, cells infected with SARS-CoV-2 experience endoplasmic reticulum stress, triggering an unfolded protein response and caspase-mediated apoptosis, a natural host defense system that halts virion production. Apoptosis of infected cells can be selectively induced by treatment with apoptosis-modulating BH3 mimetic drugs. Notably, epithelial cells within young lungs and airways are more primed to undergo apoptosis than those in adults, which may naturally hinder virion production and support milder COVID-19 severity.