Since Top2α is required to remove DNA supercoiling generated during cell proliferation, and Top2cc can become trapped during gene transcription to cause Top2cc-linked PDB due to TDP2 depletion21,22, we hypothesized that DNA topology in T cells may be affected during viral infections to trigger DDR as a mechanism of virus-induced immune evasion, and thus, persistent infection. Here, TDP2 is linked to viral infectious disease.