Type I interferon and MAVS signaling restricts chikungunya virus heart infection and cardiac tissue damage
Noval, M. G.; Bartnicki, E.; Spector, S. N.; Izzo, F.; Damani-Yokota, P.; Narula, N.; Yeung, S. T.; Rodriguez-Rodriguez, B. A.; Dewan, M. Z.; Mezzano, V.; Loomis, C.; Khanna, K. M.; Stapleford, K. A.
Show abstract
Chikungunya virus (CHIKV) infection has been associated with severe cardiac manifestations, yet, how CHIKV infection leads to heart disease remains unknown. Here, we leveraged both mouse models and human primary cells to define the mechanisms of CHIKV heart infection. We found that CHIKV actively replicates in cardiac fibroblasts and is cleared without significant tissue damage through the induction of a local type-I interferon response from both infected and non-infected cardiac cells. Importantly, signaling through the mitochondrial antiviral-signaling protein (MAVS) is required for viral clearance from the heart. In the absence of MAVS, persistent infection leads to focal myocarditis and major vessel vasculitis persisting for up to 60 days post-infection, suggesting CHIKV can lead to vascular inflammation and potential long-lasting cardiovascular complications. This study provides a model of CHIKV cardiac infection and mechanistic insight into CHIKV-induced heart disease, underscoring the importance of monitoring cardiac function in patients with CHIKV infections.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- ACE2 is the critical in vivo receptor for SARS-CoV-2 in a novel COVID-19 mouse model with TNF- and IFNγ-driven immunopathology 95%
- Cytotoxic CD4+ T cells driven by T-cell intrinsic IL-18R/MyD88 signaling predominantly infiltrate Trypanosoma cruzi-infected hearts 93%
- A hierarchy of cell death pathways confers layered resistance to shigellosis in mice 92%
Similar papers in this journal
- Zika virus spreads through infection of lymph node-resident macrophages 94%
- Single-cell-resolved interspecies comparison identifies a shared inflammatory axis and a dominant neutrophil-endothelial program in severe COVID-19 94%
- MHC class Ia molecules facilitate MCK2-dependent MCMV infection of macrophages and virus dissemination to the salivary gland 93%
Similar papers in this journal
Similar papers in this journal
- Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19 93%
- The genetic driver of Acute Necrotizing Encephalopathy, RANBP2, regulates the inflammatory response to Influenza A virus infection 93%
- B.1.1.7 and B.1.351 variants are highly virulent in K18-ACE2 transgenic mice and show different pathogenic patterns from early SARS-CoV-2 strains 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.