Human Endogenous Retrovirus K10 Encodes a Functional Integrase

We cloned a human endogenous retrovirus K10 DNA fragment encoding integrase and expressed it as a fusion protein with Escherichia coli maltose-binding protein. Integrase activities were measured in vitro by using a double-stranded oligonucleotide as a substrate mimicking viral long terminal repeats (LTR). The fusion protein was highly active for both terminal cleavage and strand transfer in the presence of Mn21 on the K10 LTR substrate. It was also active on both Rous sarcoma virus and human immunodeficiency virus type 1 LTR substrates, whereas Rous sarcoma virus and human immunodeficiency virus type 1 integrases were active only on their corresponding LTR substrates. The results strongly suggest that K10 encodes a functional integrase with relaxed substrate specificity. Human endogenous retroviruses (HERVs) constitute a group of DNA elements identified in the human genome by their homology to vertebrate retroviruses (3–5, 16, 17, 19, 20, 22–25, 27, 30). There seem to exist at least six different se-quence families with various degrees of homology among each other (5, 8, 20). The HERV-K family, whose members contain primer-binding sites for tRNALys, consists of approximately 3