GSE204689
MAVS signaling is required for preventing persistent chikungunya heart infection and chronic vascular tissue inflammation
Chikungunya virus (CHIKV) infection has been associated with severe cardiac manifestations. However, how CHIKV infection leads to heart disease remains unknown. Here, using C57BL/6 mice we show that cardiac fibroblasts are the main target of CHIKV infection in the heart, and that cardiac tissue infection induces activation of the type I interferon (IFN-I) pathway in both infected and non-infected cardiac cells. The loss of IFN-I signaling results in increased CHIKV infection, virus spreading, and apoptosis in cardiac tissue. Importantly, signaling through the mitochondrial antiviral-signaling protein (MAVS) is essential for efficient CHIKV clearance from the heart. Indeed, persistent infection in cardiac tissue of MAVS-deficient mice leads to cardiac damage characterized by focal myocarditis and major vessel vasculitis. This study provides mechanistic insight on how CHIKV can lead to cardiac damage, underscoring the importance of monitoring cardiac function in patients with CHIKV infections. Overall design: For bulk RNA-sequencing male mice were infected intravenously with 10^5 PFU of CHIKV Indian Ocean lineage (IOL) or HI control, and heart were collected at 2 and 5 dpi (days post-infection). Hearts were collected in 500 µl of TRIzolTM (Invitrogen) with one 5 mm stainless steel bead and processed as described above. RNA was extracted using Zymo direct-zol RNA purification kit (Zymo research, #R2072) according to the manufacturer's instructions. A total of 500 ng per sample was sent to the NYU Genome Technology Center for quality control assessment, automated TruSeq stranded total RNA, with RiboZero Gold library preparation and Illumina Novaseq6000 sequencing (single pair 100).