emtricitabine--tenofovir-disoproxil-fumarate-drug-combination and Myocarditis

Topics: Anti-HIV Agents; Arrhythmias, Cardiac; Autopsy; Coronary Angiography; Creatine Kinase; Deoxycytidine; Drug Combinations; Electrocardiography; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Fatal Outcome; HIV Infections; Humans; Lopinavir; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Muscular Diseases; Myocarditis; Myocardium; Organophosphorus Compounds; Pulmonary Edema; Ritonavir

Both Aicardi-Goutières syndrome, a Mendelian mimic of congenital infection, and the autoimmune disease systemic lupus erythematosus can result from mutations in the gene encoding the enzyme Trex1. In mice, the absence of Trex1 causes severe myocarditis. The enzyme is thought to degrade endogenous retroelements, thus linking them to autoimmune disease. However, inhibition of reverse transcription by the inhibitor zidovudine (AZT) did not ameliorate the disease, weakening the link to retroelements.. Here, we show that two other FDA-approved drugs that inhibit reverse transcriptase can ameliorate the myocarditis in Trex1-null mouse.. The result suggests that retroelements contribute to this hereditary form of autoimmunity, and that treatment with retroelement inhibitors might ameliorate Aicardi-Goutières syndrome in humans.

Topics: Animals; Autoimmune Diseases; Autoimmune Diseases of the Nervous System; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Exodeoxyribonucleases; Green Fluorescent Proteins; Lupus Erythematosus, Systemic; Mice; Mice, Knockout; Myocarditis; Nervous System Malformations; Nevirapine; Organophosphorus Compounds; Phosphoproteins; Retroelements; Reverse Transcriptase Inhibitors; Zidovudine