STRUCTURE AND GENOMIC ORGANIZATION OF A NOVEL HUMAN ENDOGENOUS RETROVIRUS FAMILY - HERV-K (HML-6)

Prototypic elements of a novel human endogenous retrovirus (HERV) fami ly were identified and cloned from a human genomic library by the use of a pol fragment, HML-6, related to type A and type B retroviruses an d class II HERVs. Out of 39 pol-hybridizing clones, five contained str uctures of full-length retroviral proviruses, with regions showing sim ilarity to gag, pol and env, flanked by long terminal repeats (LTRs). Restriction mapping and partial sequence analysis of each full-length clone revealed few conserved restriction sites among HML-6 genomes, an d about 20% sequence divergence over the reverse transcriptase region sequenced, suggesting that HML-6 constitutes a heterogeneous, but dist inct family of elements belonging to the HERV-K superfamily. Sequence analysis of two clones, HML-6p and HML-6.17, revealed a lysine (K) tRN A UUU primer-binding site, and 40-68% nucleotide sequence similarity t o LTR, gag, pro, pol and env regions of type B retroviruses and class II HERVs. HERV-K (HML-6) elements are present at about 30-40 copies pe r haploid genome. The HML-6 LTRs contain putative progesterone-respons ive elements, which may be involved in the regulation of HML-6 express ion. Furthermore, there are about 50 additional solitary HML-6 LTRs pe r haploid genome. Such LTRs were integrated within the pol region of t wo clones belonging to the same HML-6 family, indicating that some sit e preference may be involved in HERV integration.