Identification of human endogenous retroviruses with complex mRNA expression and particle formation.

Abstract

Retroviruses comprise strains with considerable disease potential in animals and humans. In addition to exogenous strains transmitted horizontally, endogenous proviruses are transmitted through the germ line. Some of these endogenous retroviruses can be pathogenic in mice and possibly in other animal species. They may also be considered as mobile genetic elements with the potential to produce mutations. In humans, genomic DNA contains numerous endogenous retroviral sequences detected by their partial relatedness to animal retroviruses. However, all proviruses sequenced so far have been found to be defective. In this communication, we describe the expression of a family of human endogenous retrovirus sequences (HERV-K) in GH cells, a teratocarcinoma cell line producing the human teratocarcinoma-derived retrovirus (HTDV) particles previously described by us. Four viral mRNA species could be identified, including a full-length mRNA. The other three subgenomic mRNAs are generated by single or double splicing events. This expression pattern is reminiscent of the more complex control of virus gene regulation observed, for example, with lenti-or spumavirus strains, although HERV-K shows no sequence homology to human T-lymphotropic virus or human immunodeficiency virus. Sequence analysis of expressed HERV-K genomes revealed nondefective gag genes, a prerequisite for particle formation. Open reading frames were also observed in pol and env. Antisera raised against recombinant gag proteins of HERV-K stained HTDV particles in immunoelectron microscopy, linking them to the HERV-K family.

Human endogenous retrovirus protein cORF supports cell transformation and associates with the promyelocytic leukemia zinc finger protein

“…The vast majority of HERV sequences are dysfunctional due to the accumulation of multiple nonsense mutations. However, proviral loci of the HERV-K (HML-2) family of retroviral elements, of which 30 to 50 copies are estimated to reside in the haploid human genome, often contain intact open reading frames for the viral proteins Gag, Prt, Pol and Env (Lower et al, 1993;Mayer et al, 1997a,b). We have recently identi®ed an almost intact HERV-K provirus on human chromosome 7 (Mayer et al, 1999).…”

“…Germ cell tumors (GCTs) and GCT cell lines express complex splicing patterns of HERV-K (HML-2) transcripts reminiscent of the patterns observed upon infection with exogenous lentiviruses (Lower et al, 1993). GCTs produce large quantities of Gag protein (Sauter et al, 1995) and up to 85% of the patients with GCT produce antibodies directed against the viral Env protein whereas healthy individuals and patients with in¯ammatory diseases or tumors other than GCT very rarely develop such antibodies.…”

Characterization of the human endogenous retrovirus K proteinase

“…Expression ofpT7-pro0.7 in E. coli BL21DE3 resulted in the autocatalytic cleavage of the pT7-pro0. (Ono et al, 1986;Mueller-Lantzsch et al, 1993;L6wer et al, 1993). All constructs except pT7-pro0.7 and pSPTgag-prot were expressed as TrpE fusion proteins in E. coli.…”

Search for active endogenous retroviruses: identification and characterization of a HERV-E gene that is expressed in the pancreas and thyroid

“…In the present study, we have applied this strategy to the HERV-E family and have identified an active locus that is expressed in normal pancreas and thyroid tissues with enough transcripts for detection by Northern blot hybridization. The expression of HERVs is usually strictly suppressed in normal tissues, and has previ- ously been primarily observed in various tumors and tumor cell lines or predominantly in the placenta among normal tissues (Kato et al 1987;Kjellman et al 1999;Löwer et al 1993Löwer et al , 1996. Therefore, this is, to the best of our knowledge, the first report of predominant expression of HERV in normal tissues other than placenta.…”