This study characterizes HERV-K (HML-6), a novel family of human endogenous retroviruses. Researchers isolated and cloned full-length HML-6 proviruses from a human genomic library using a pol fragment probe. Five clones contained complete retroviral structures with gag, pol, and env regions flanked by long terminal repeats (LTRs). Analysis revealed HML-6 elements form a heterogeneous but distinct class II HERV family with approximately 20% sequence divergence in the reverse transcriptase region. The HML-6 genome is approximately 6.9 kb in size and contains lysine tRNA primer-binding sites. Sequence analysis showed 40-68% nucleotide similarity to type B retroviruses and other class II HERVs. The HML-6 LTRs contain putative progesterone-responsive elements potentially regulating expression. Southern blot analysis indicated humans carry approximately 30-40 HML-6 copies per haploid genome, plus about 50 additional solitary LTRs. Notably, solitary LTRs were found integrated within the pol region of some clones, suggesting site preference in HERV integration. All identified HML-6 elements contained deletions and mutations disrupting coding regions.

Key findings

• HERV-K (HML-6) represents a distinct class II HERV family with 30-40 copies per haploid human genome, plus approximately 50 solitary LTRs
• HML-6 elements are heterogeneous proviruses approximately 6.9 kb in size containing gag, pol, and env regions with 20% sequence divergence in reverse transcriptase
• HML-6 LTRs contain putative progesterone-responsive elements that may regulate expression and show 40-68% nucleotide similarity to type B retroviruses
• All HML-6 elements contain deletions, nonsense mutations, and frameshifts in coding regions, indicating they are likely defective retroviruses
• Solitary HML-6 LTRs integrate preferentially within pol regions, suggesting site-specific integration mechanisms