Development of Insulin-Dependent Diabetes Mellitus Does Not Depend on Specific Expression of the Human Endogenous Retrovirus HERV-K

Abstract

patients. Here we present findings contradicting this intriguing hypothesis. Autoimmunity and Transplantation Division The Walter and Eliza Hall The Endogenous IDDMK 1,2 22 Provirus Is Not a Novel Retrovirus Institute of Medical Research Royal Melbourne Hospital HERV-K is an endogenous retrovirus family of old world monkeys and humans with homologies to type B and Parkville 3050 Australia D retroviruses. Within the approximately 50 proviral copies of this HERV family only very few of the full-length William A. Rudert, Patrizia Luppi, genomes (designated type 2) have retained colinear coding capacity. As this HERV family codes for the hu-and Massimo Trucco Division of Immunogenetics man teratocarcinoma-derived retrovirus (HTDV), it was tentatively designated HTDV/HERV-K to discriminate it Department of Pediatrics University of Pittsburgh from other MMTV-related HERV families with primerbinding sites for tRNA lysine (HERV-K). A subclass of School of Medicine and Children's Hospital Pittsburgh, Pennsylvania 15213 HTDV/HERV-K proviruses (type 1) is characterized by a deletion affecting the C terminus of the integrase domain Alessandra Fierabracci, Paul Andrew Biro, and the amino terminus of the envelope (Env), the signal peptide region (reviewed by Lo ¨wer et al., 1996). The and Gian Franco Bottazzo* † Department of Immunology deletion also eliminates the first exon of the corf gene, an accessory gene that enhances the expression of St Bartholomew's and the Royal London School of Medicine and Dentistry structural proteins. This function is lacking in cell types in which only type 1 proviruses are expressed. In addi-Turner Street, London E1 2AD United Kingdom tion, many type 1 proviruses do not exhibit env splicing (Lo ¨wer et al., 1995). Most of the HTDV/HERV-K provi-* The Autoimmune Diseases Charitable Trust 28 Glenilla Road ruses carry stop codons in their env genes preventing expression of functional Env proteins. Sequence com-London NW3 4AN United Kingdom parison clearly shows that the truncated IDDMK 1,2 22 env sequence identified by Conrad et al. stems from one of these proviruses. It is a type 1 element similar to the References proviruses K10 and K18 described previously (Ono, 1986).

Establishment and Characterization of Molecular Clones of Porcine Endogenous Retroviruses Replicating on Human Cells

“…For instance, in the HERV-K family, which comes closest of all known HERV to encoding infectious virus, no corresponding replication-competent virus could be found in the human genome (66). Nevertheless, expression of types B and D HERV-K full-length mRNAs was observed in numerous tissues (40). As PERV belong to the C-type retroviruses, related HERV sequences might offer targets for recombination.…”

Retroviruses and the pathogenesis of schizophrenia

“…However, the reported isolation of a previously unknown HERV from a patient with diabetes and the identification of one of its proteins as a putative superantigen (10) have not been confirmed in subsequent studies (11)(12)(13). In addition, sequences of endogenous retroviruses nearly identical to multiple sclerosisassociated retrovirus seem to be expressed in control human tissue (14).…”

Isolation and localization of an IDDMK1,2-22-related human endogenous retroviral gene, and identification of a CA repeat marker at its locus

“…Therefore, it is also possible that all three sequences (our HERV, HERV-K18, and IDDMK1,2-22) are the representatives of the same single gene. While the involvement of IDDMK1,2-22 in the pathogenesis of type 1 diabetes is controversial (Lan et al 1998;Lower et al 1998;Murphy et al 1998;Muir et al 1999), it is interesting that the gene was mapped to chromosome 1q21.3-q22 regardless of whether it is the genomic sequence corresponding to IDDMK1,2-22. Recent study in IDDM families from the United Kingdom detected several regions with more than 1.5 of maximum lod score (MLS) that have not been reported previously (Mein et al 1998).…”