ABSTRACT
IMPORTANCE: Clinical data suggest that Hepatitis C virus (HCV) levels are generally lower in Hepatitis B virus (HBV) co-infected patients, but the mechanism is unknown. Here, we show that HBV, but not HCV, activated absent in melanoma-2. This in turn results in inflammasome-mediated cleavage of pro-IL-18, leading to an innate immune activation cascade that results in increased interferon-γ, suppressing both viruses.
Subject(s)
Coinfection , DNA-Binding Proteins , Hepacivirus , Hepatitis B virus , Hepatitis B , Hepatitis C , Immunity, Innate , Humans , Coinfection/immunology , Coinfection/virology , DNA-Binding Proteins/metabolism , Hepacivirus/immunology , Hepatitis B/complications , Hepatitis B/immunology , Hepatitis B/virology , Hepatitis B virus/immunology , Hepatitis B virus/physiology , Hepatitis C/complications , Hepatitis C/immunology , Hepatitis C/virology , Inflammasomes/metabolism , Interferon-gamma/immunologyABSTRACT
Infection with SARS-CoV-2, the causative agent of COVID-19, causes mild to moderate disease in most patients but carries a risk of morbidity and mortality. Seriously affected individuals manifest disorders of hemostasis and a cytokine storm, but it is not understood how these manifestations of severe COVID-19 are linked. Here, we showed that the SARS-CoV-2 spike protein engaged the CD42b receptor to activate platelets via 2 distinct signaling pathways and promoted platelet-monocyte communication through the engagement of P selectin/PGSL-1 and CD40L/CD40, which led to proinflammatory cytokine production by monocytes. These results explain why hypercoagulation, monocyte activation, and a cytokine storm are correlated in patients severely affected by COVID-19 and suggest a potential target for therapeutic intervention.
