SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition

PJ Mullen, G Garcia Jr, A Purkayastha… - Nature …, 2021 - nature.com
PJ Mullen, G Garcia Jr, A Purkayastha, N Matulionis, EW Schmid, M Momcilovic, C Sen
Nature communications, 2021nature.com
Viruses hijack host cell metabolism to acquire the building blocks required for replication.
Understanding how SARS-CoV-2 alters host cell metabolism may lead to potential
treatments for COVID-19. Here we profile metabolic changes conferred by SARS-CoV-2
infection in kidney epithelial cells and lung air-liquid interface (ALI) cultures, and show that
SARS-CoV-2 infection increases glucose carbon entry into the TCA cycle via increased
pyruvate carboxylase expression. SARS-CoV-2 also reduces oxidative glutamine …
Abstract
Viruses hijack host cell metabolism to acquire the building blocks required for replication. Understanding how SARS-CoV-2 alters host cell metabolism may lead to potential treatments for COVID-19. Here we profile metabolic changes conferred by SARS-CoV-2 infection in kidney epithelial cells and lung air-liquid interface (ALI) cultures, and show that SARS-CoV-2 infection increases glucose carbon entry into the TCA cycle via increased pyruvate carboxylase expression. SARS-CoV-2 also reduces oxidative glutamine metabolism while maintaining reductive carboxylation. Consistent with these changes, SARS-CoV-2 infection increases the activity of mTORC1 in cell lines and lung ALI cultures. Lastly, we show evidence of mTORC1 activation in COVID-19 patient lung tissue, and that mTORC1 inhibitors reduce viral replication in kidney epithelial cells and lung ALI cultures. Our results suggest that targeting mTORC1 may be a feasible treatment strategy for COVID-19 patients, although further studies are required to determine the mechanism of inhibition and potential efficacy in patients.
nature.com
以上显示的是最相近的搜索结果。 查看全部搜索结果