HERV-K - THE BIOLOGICALLY MOST ACTIVE HUMAN ENDOGENOUS RETROVIRUS FAMILY

The human genome contains a wide variety of endogenous retrovirus-like sequences. The human endogenous retrovirus type K (HERV-K) family com prises 30-50 members per haploid genome in humans and is highly conser ved in Old World monkeys and apes. Some proviruses are displaying open reading frames (ORF) with coding capacity for viral particles. HERV-K sequences most likely code for the previously described human teratoc arcinoma-derived virus (HTDV) and correlated expression of HERV-K Gag has been demonstrated by immunoelectron microscopy studies. Protease, but not yet reverse transcriptase (RT), enzymatic activity was demonst rated for recombinant HERV-K proteins. However, an ultrasensitive RT a ssay revealed specific polymerase activity associated with the HTDV pa rticles. HERV-K transcription is specifically regulated by viral long terminal repeats and RNA is expressed at low steady-state levels in a variety of human tissues and rumours. In teratocarcinoma cell lines, H ERV-K is highly expressed in a complex pattern showing full-length as well as subgenomic envelope (env) and two alternatively spliced small transcripts. The doubly spliced 1.8-kb mRNA codes for cORF protein whi ch resembles Rev of HIV-I and is located in the nucleolus. In addition , the cORF sequence acts as a leader and is essential for effective ex pression of glycosylated HERV-K Env protein. Although HERV-K sequences code for all necessary retroviral proteins, infectious particles coul d not yet be demonstrated. The putative implication of HERV sequences in pathophysiological processes, for example, testicular malignancies, remains to be elucidated.