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Magnitude and timing of the antiviral response determine SARS-CoV-2 replication early in infection
- Source :
- The Journal of Experimental Medicine, medRxiv, article-version (status) pre, article-version (number) 2
- Publication Year :
- 2021
- Publisher :
- Cold Spring Harbor Laboratory, 2021.
-
Abstract
- SARS-CoV-2 replication in the upper respiratory tract initiates infection and leads to viral transmission. Cheemarla et al. show that a dynamic innate immune response can curtail viral replication early in infection, and that recent exposure to rhinovirus accelerates innate defenses and blocks viral replication.<br />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.<br />Graphical Abstract
- Subjects :
- Innate immune system
viruses
Innate Immunity and Inflammation
fungi
food and beverages
virus diseases
Heterologous
respiratory system
Biology
medicine.disease_cause
Virology
Article
respiratory tract diseases
Infectious Disease and Host Defense
Viral replication
Interferon
Replication (statistics)
medicine
Doubling time
Rhinovirus
Covid-19
Gene
medicine.drug
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- The Journal of Experimental Medicine, medRxiv, article-version (status) pre, article-version (number) 2
- Accession number :
- edsair.doi.dedup.....a5f408c0b8201c4d869577f51810be0a