Structure and genomic organization of a novel human endogenous retrovirus family: HERV-K (HML-6).
Prototypic elements of a novel human endogenous retrovirus (HERV) family 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 and class II HERVs. Out of 39 polhybridizing clones, five contained structures of full-length retroviral proviruses, with regions showing similarity 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, and about 20% sequence divergence over the reverse transcriptase region sequenced, suggesting that HML-6 constitutes a heterogeneous, but distinct family of elements belonging to the HERV-K superfamily. Sequence analysis of two clones, HML-6p and HML-6.17, revealed a lysine (K) tRNA UUU primer-binding site, and 40-68% nucleotide sequence similarity to 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 per haploid genome. The HML-6 LTRs contain putative progesterone-responsive elements, which may be involved in the regulation of HML-6 expression. Furthermore, there are about 50 additional solitary HML-6 LTRs per haploid genome. Such LTRs were integrated within the pol region of two clones belonging to the same HML-6 family, indicating that some site preference may be involved in HERV integration.
Medstrand
P
P
Department of Medical Microbiology, Lund University, Sweden. Patrik.Medstrand@mmb.lu.se
Mager
D L
DL
Yin
H
H
Dietrich
U
U
Blomberg
J
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004279:DNA, Viral; D017988:Gammaretrovirus / Q000145:classification / Q000235:genetics*; D015752:Genes, env; D015750:Genes, gag; D015751:Genes, pol; D014644:Genetic Variation; D016679:Genome, Viral; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D012091:Repetitive Sequences, Nucleic Acid
D004279:DNA, Viral