Prevention of inflammation by anti-retroviral drugs

Aicardi-Goutières syndrome (AGS) is a genetically determined encephalopathy with remarkable phenotypic overlap with the sequelae of congenital infection. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies that target nucleic acids and their associated proteins. Like AGS, SLE is associated with a perturbation of type I interferon metabolism. Both AGS and a cutaneous subtype of SLE called familial chilblain lupus can result from mutations in TREX1. Furthermore, mutations in TREX1 represent the single most common cause of monogenic SLE identified to date.

Trex1-deficient mice suffer from inflammation of the heart muscle and glomerulonephritis. The disease takes an aggressive course, with mice starting to die after 4 weeks of age. On the basis that unrestricted retroelements may cause, or at least contribute to, the disease, we reasoned that it ought to be possible to treat or prevent disease with anti-retroviral agents. Indeed, we could prevent the autoimmune disease with a Truvada/­Viramune combination (both FDA-approved drugs), which ought to inhibit both classes of retroelements—retroviruses and retrotrans­po­sons. We now investigate whether such drugs are also beneficial in B/W mice, which succumb to “spontaneous” lupus.

In collaboration with Dr. Dan Eilat, University of Jerusalem.