DENV-4 infection suppresses transcription of DNA repair genes

The molecular mechanisms behind Dengue virus-dependent host pathogenesis, especially genome instability, remain largely unclear. This RNA virus causes a debilitating disease during active infection and presents future risks of postdengue syndromes, leukemia, and DNA damage in the blood cells of infected patients, with the underlying mechanisms unknown. In this study, we show that DENV-4 infection induces significant DNA damage and suppresses the transcription of genes involved in DNA repair and select mutagenic translesion synthesis (TLS) polymerases, indicating that DENV-4-dependent pathobiology leaves durable biological “scars” that incrementally increase chronic disease risk, including carcinogenesis and postdengue syndromes.