Therefore, TRF2-mediated telomere uncapping and the resulting telomere loss-driven cell cycle arrest in the early stage of viral infections may function as a double-edged sword, explaining both the overwhelming cell death storm in acute infection, and the immune tolerance or immunosuppression in chronic/persistent infection; whereas lengthened and damaged telomeres are associated with cell chromosomal rearrangement and tumors (66). Here, TERF2 is linked to viral infectious disease.