IDENTIFICATION OF HUMAN ENDOGENOUS RETROVIRUSES WITH COMPLEX MESSENGER-RNA EXPRESSION AND PARTICLE FORMATION

Retroviruses comprise strains with considerable disease potential in a nimals and humans. In addition to exogenous strains transmitted horizo ntally, endogenous proviruses are transmitted through the germ line. S ome of these endogenous retroviruses can be pathogenic in mice and pos sibly in other animal species. They may also be considered as mobile g enetic elements with the potential to produce mutations. In humans, ge nomic DNA contains numerous endogenous retroviral sequences detected b y their partial relatedness to animal retroviruses. However, all provi ruses sequenced so far have been found to be defective. In this commun ication, we describe the expression of a family of human endogenous re trovirus sequences (HERV-K) in GH cells, a teratocarcinoma cell line p roducing the human teratocarcinoma-derived retrovirus (HTDV) particles previously described by us. Four viral mRNA species could be identifi ed, including a full-length mRNA. The other three subgenomic mRNAs are generated by single or double splicing events. This expression patter n is reminiscent of the more complex control of virus gene regulation observed, for example, with lenti- or spumavirus strains, although HER V-K shows no sequence homology to human T-lymphotropic virus or human immunodeficiency virus. Sequence analysis of expressed HERV-K genomes revealed non-defective gag genes, a prerequisite for particle formatio n. Open reading frames were also observed in pol and env. Antisera rai sed against recombinant gag proteins of HERV-K stained HTDV particles in immunoelectron microscopy, linking them to the HERV-K family.