Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics

Initial replication of SARS-CoV-2 in the upper respiratory tract is required to establish infection, and the replication level correlates with the likelihood of viral transmission. Here, we examined the role of host innate immune defenses in restricting early SARS-CoV-2 infection using transcriptomi...

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Vydáno v:The Journal of experimental medicine Ročník 218; číslo 8
Hlavní autoři: Cheemarla, Nagarjuna R, Watkins, Timothy A, Mihaylova, Valia T, Wang, Bao, Zhao, Dejian, Wang, Guilin, Landry, Marie L, Foxman, Ellen F
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 02.08.2021
Témata:
Adult
Aged
Aged, 80 and over
Angiotensin-Converting Enzyme 2 - genetics
Case-Control Studies
Chemokine CXCL10 - metabolism
COVID-19 - immunology
COVID-19 - virology
Disease Susceptibility - immunology
Female
Gene Expression Profiling
Host-Pathogen Interactions - physiology
Humans
Immunity, Innate - physiology
Interferons - genetics
Interferons - immunology
Interferons - metabolism
Male
Middle Aged
Nasopharynx - virology
Picornaviridae Infections - immunology
Picornaviridae Infections - virology
SARS-CoV-2 - genetics
SARS-CoV-2 - physiology
Viral Load
Virus Replication
ISSN:1540-9538, 1540-9538
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Shrnutí:Initial replication of SARS-CoV-2 in the upper respiratory tract is required to establish infection, and the replication level correlates with the likelihood of viral transmission. Here, we examined the role of host innate immune defenses in restricting early SARS-CoV-2 infection using transcriptomics and biomarker-based tracking in serial patient nasopharyngeal samples and experiments with airway epithelial organoids. SARS-CoV-2 initially replicated exponentially, with a doubling time of ∼6 h, and induced interferon-stimulated genes (ISGs) in the upper respiratory tract, which rose with viral replication and peaked just as viral load began to decline. Rhinovirus infection before SARS-CoV-2 exposure accelerated ISG responses and prevented SARS-CoV-2 replication. Conversely, blocking ISG induction during SARS-CoV-2 infection enhanced viral replication from a low infectious dose. These results show that the activity of ISG-mediated defenses at the time of SARS-CoV-2 exposure impacts infection progression and that the heterologous antiviral response induced by a different virus can protect against SARS-CoV-2.
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ISSN:1540-9538
1540-9538
DOI:10.1084/jem.20210583