دورية أكاديمية

Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release

التفاصيل البيبلوغرافية
العنوان: Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release
المؤلفون: Labzin, Larisa I., Chew, Keng Yih, Eschke, Kathrin, Wang, Xiaohui, Esposito, Tyron, Stocks, Claudia J., Rae, James, Patrick, Ralph, Mostafavi, Helen, Hill, Brittany, Yordanov, Teodor E., Holley, Caroline L., Emming, Stefan, Fritzlar, Svenja, Mordant, Francesca L., Steinfort, Daniel P., Subbarao, Kanta, Nefzger, Christian M., Lagendijk, Anne K., Gordon, Emma J., Parton, Robert G., Short, Kirsty R., Londrigan, Sarah L., Schroder, Kate
المصدر: Science Signaling ; volume 16, issue 782 ; ISSN 1945-0877 1937-9145
بيانات النشر: American Association for the Advancement of Science (AAAS)
سنة النشر: 2023
الوصف: Macrophages are key cellular contributors to the pathogenesis of COVID-19, the disease caused by the virus SARS-CoV-2. The SARS-CoV-2 entry receptor ACE2 is present only on a subset of macrophages at sites of SARS-CoV-2 infection in humans. Here, we investigated whether SARS-CoV-2 can enter macrophages, replicate, and release new viral progeny; whether macrophages need to sense a replicating virus to drive cytokine release; and, if so, whether ACE2 is involved in these mechanisms. We found that SARS-CoV-2 could enter, but did not replicate within, ACE2-deficient human primary macrophages and did not induce proinflammatory cytokine expression. By contrast, ACE2 overexpression in human THP-1–derived macrophages permitted SARS-CoV-2 entry, processing and replication, and virion release. ACE2-overexpressing THP-1 macrophages sensed active viral replication and triggered proinflammatory, antiviral programs mediated by the kinase TBK-1 that limited prolonged viral replication and release. These findings help elucidate the role of ACE2 and its absence in macrophage responses to SARS-CoV-2 infection.
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1126/scisignal.abq1366
الإتاحة: https://doi.org/10.1126/scisignal.abq1366Test
رقم الانضمام: edsbas.753DADFD
قاعدة البيانات: BASE