Upon infection, the levels of HBV cccDNA and core protein were markedly lower in HepG2-NTCP cells with LIG1 or LIG3 knock-down compared to the control knock-down cells (Fig 6B, 6C and 6D), suggesting that LIG1 and LIG3 are also required for the first round HBV cccDNA formation during de novo infection. Here, LIG1 is linked to infection.