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https://hdl.handle.net/20.500.12008/42841
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Title: | Delayed engagement of host defenses enables SARSCoV-2 viremia and productive infection of distal organs in the hamster model of COVID-19 |
Authors: | Carrau Eguía, Lucía Frere, Justin J. Golynker, Ilona Fajardo Rossi, Álvaro Rivera, Cristobal F. Horiuchi, Shu Roonprapunt, Tyler Minkoff, Judith M. Blanco-Melo, Daniel TenOever, Benjamin |
Type: | Artículo |
Keywords: | SARS-CoV-2, COVID-19, Immune defense |
Issue Date: | 2023 |
Abstract: | Clinical presentations that develop in response to infection result from interactions between the pathogen and
host defenses. SARS-CoV-2, the etiologic agent of COVID-19, directly antagonizes these defenses, leading to
delayed immune engagement in the lungs that materializes only as cells succumb to infection and are phagocytosed. Leveraging the golden hamster model of COVID-19, we sought to understand the dynamics between SARS-CoV-2 infection in the airways and the systemic host response that ensues. We found that early SARS-CoV2 replication was largely confined to the respiratory tract and olfactory system and, to a lesser extent, the heart and gastrointestinal tract but generated a host antiviral response in every organ as a result of circulating type I and III interferons. Moreover, we showed that diminishing the response in the airways by immunosuppression or administration of SARS-CoV-2 intravenously resulted in decreased immune priming, viremia, and increased viral tropism, including productive infection of the liver, kidney, spleen, and brain. Last, we showed that productive infection of the airways was required for mounting an effective and system-wide antiviral response. Together, these data illustrate how COVID-19 can result in diverse clinical presentations in which disease outcomes can be a by-product of the speed and strength of immune engagement. These studies provide additional evidence for the mechanistic basis of the diverse clinical presentations of COVID-19 and highlight the ability of the respiratory tract to generate a systemic immune defense after pathogen recognition. |
Publisher: | American Association for the Advancement of Science |
IN: | Science Signaling, 2023, 16(789): eadg5470. |
Citation: | Carrau Eguía, L, Frere, J, Golynker, I [y otros autores]. "Delayed engagement of host defenses enables SARSCoV-2 viremia and productive infection of distal organs in the hamster model of COVID-19". Science Signaling. [en línea] 2023, 16(789): eadg5470. 13 h. DOI: 10.1126/scisignal.adg5470. |
ISSN: | 1937-9145 |
Appears in Collections: | Publicaciones académicas y científicas - Facultad de Ciencias |
Files in This Item:
File | Description | Size | Format | ||
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10.1126.scisignal.adg5470.pdf | 1,45 MB | Adobe PDF | View/Open |
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