Considering that HBV cccDNA is synthesized from both the rcDNA from incoming virions and the newly synthesized rcDNA during natural infection [8,63], to specifically study the effect of TRIM65 on the preexisting cccDNA transcription in the context of HBV infection, the HBV-infected HepG2-NTCP scramble KO and TRIM65 KO cells were treated with 3TC to block de novo HBV-replication-mediated cccDNA replenishment. The gene discussed is TRIM65; the disease is infection.