Endogenous retrovirus ERV-DC8 highly integrated in domestic cat populations is a replication-competent provirus

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections in vertebrate genomes and are inherited by offspring. ERVs can produce pathogenic viruses through gene mutations or recombination. ERVs in domestic cats (ERV-DCs) generate feline leukemia virus subgroup D (FeLV-D) through viral recombination. Herein, we characterized the locus ERV-DC8, on chromosome B1, as an infectious replication-competent provirus. ERV-DC8 infected several cell lines, including human cells. Transmission electron microscopy of ERV-DC8 identified the viral release as a Gammaretrovirus. ERV-DC8 was identified as the FeLV-D viral interference group, with feline copper transporter 1 as its viral receptor. Insertional polymorphism analysis showed high ERV-DC8 integration in domestic cats. This study highlights the role, pathogenicity, and evolutionary relationships between ERVs and their hosts.