An aberrant resurrection of endogenous retrovirus prompts acute myocarditis and heart failure
The abberant resurgence of which have been recently found to link to some critical pathologies. To evaluate the occurrence and role of ERV resurrgenece in heart and heart failure (HF), we conducted heart total RNA-seq analysis from mice ischemia-reperfusion (I/R) heart failure models and found that ERVs were activated which is similar in various cross-species models of heart failure. To explore the mechanism of ERVs resurgence we profiled trimethylation at lysine 9 of histone H3 (H3K9me3) ChIP- and MeRIP-seq of cardiomyocytes specific TRIM28 knockout mice heart. The deprivation of TRIM28 in the mouse myocardium attenuated the epigenetic surveillance of H3K9me3 and N6-methyladenosine (m6A), and revived the ERVs, which consequently activated the intracellular antiviral innate immune pathways of TLR7-9 and NF-kappaB and lead to the myocarditis and acute heart failure. Overall design: For total RNA-seq of I/R mice, ischemia was created by temporarily ligating the left anterior descending coronary artery for 45 min and reperfusion for 24h. Hearts were collected and then extracted and total RNA sequencing was performed. For total RNA-seq, H3K9me3 ChIP-seq and MeRIP-seq of TRIM28 iCKO mice, the genomic deletion of TRIM28 was introduced via an intraperitoneal administration of 25mg/kg tamoxifen dissolved in corn oil for a consecutive five days. After 1week, hearts were extracted then total RNA, ChIP and MeRIP sequencing was performed.