Human endogenous retrovirus HERV-H family in human tissues and cancer cells: expression, identification, and phylogeny

HERV-H family is the most abundant HERV families in the human genome with more than 1000 copies including full-length, truncated form, and solitary LTRs. We investigated envelope (env) gene fragments of HERV-H family in various human tissues and cancer cells. The env fragments were detected in mRNA of several human tissues (placenta, skeletal muscle, spleen, and thymus) and cancer cells (RT4, BT-474, HCT-116, TE-1, UO-31, Jurkat, HepG2, A549, MCF7, OVCAR-3, MIA-PaCa-2, PC3, LOX-IMVI, AZ521, 2F7, U-937, and C-33A) by RT-PCR approach. The RT-PCR products were cloned and sequenced. New 12 clones from human tissues and 48 clones from cancer cells of env gene sequences belonging to the HERV-H family showed 84.3–98.1% sequence similarity to that of HERV-H (AF108843). Deduced amino acid sequences of 60 clones from human tissues and cancer cell lines showed multiple frameshifts and termination codons caused by deletion/insertion or point mutation with the exception of eight clones as following: HHE9-1, HHE9-5 (skeletal muscle), HHE10-5 (spleen), CHE10-9 (MCF7), CHE12-4, CHE12-5 (MIA-PaCa-2), and CHE18-1, CHE18-3 (C-33A) to that of HERV-H (AF108843). A phylogenetic tree of the HERV-H family was constructed to understand their relationship, indicating that they were divided into three groups, one major (group I) and two minor (group II and III), through sequence divergence. The HERV-H families in group I has been proliferated on human genome during hominoid evolution. These active HERV-H elements are worthy of further investigations as potential pathogenic effects to various human diseases including cancers.