Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Viral replication in human macrophages enhances an inflammatory cascade and interferon driven chronic COVID-19 in humanized mice. Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production, viral RNA, and sustained interferon (IFN) response all of which are recapitulated and required for pathology in the SARS-CoV-2 infected MISTRG6-hACE2 humanized mouse model of COVID-19 with a human immune system1-20. Blocking either viral replication with Remdesivir21-23 or the downstream IFN stimulated cascade with anti-IFNAR2 in vivo in the chronic stages of disease attenuated the overactive immune-inflammatory response, especially inflammatory macrophages. Here, we show SARS-CoV-2 infection and replication in lung-resident human macrophages is a critical driver of disease. In response to infection mediated by CD16 and ACE2 receptors, human macrophages activate inflammasomes, release IL-1 and IL-18 and undergo pyroptosis thereby contributing to the hyperinflammatory state of the lungs. Inflammasome activation and its accompanying inflammatory response is necessary for lung inflammation, as inhibition of the NLRP3 inflammasome pathway reverses chronic lung pathology. Remarkably, this same blockade of inflammasome activation leads to the release of infectious virus by the infected macrophages. Thus, inflammasomes oppose host infection by SARS-CoV-2 by production of inflammatory cytokines and suicide by pyroptosis to prevent a productive viral cycle.
5
The categories of this paper are: cell
25
The categories of this paper are: bioengineering
16
The categories of this paper are: microbiology
19
The categories of this paper are: epidemiology
15
The categories of this paper are: developmental
18
The categories of this paper are: systems
9
The categories of this paper are: synthetic
22
The categories of this paper are: physiology
26
The categories of this paper are: biochemistry
7
The categories of this paper are: ecology
28
The categories of this paper are: communication
27
The categories of this paper are: pathology
32
The categories of this paper are: zoology
3
The categories of this paper are: evolutionary
20
The categories of this paper are: pharmacology
8
The categories of this paper are: genomics