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

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 primer-binding 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 and the amino terminus of the envelope (Env), the signal peptide region (reviewed by Lö wer et al., 1996). The 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 (Lö 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 a 3% difference to K10 in env and in the long terminal repeats (LTRs), the most variable regions of a virus, and a near identity to the LTRs of K18. In summary Conrad Nature 371, 351–355. et al. have identified one of the proviruses of a well-In human teratocarcinoma cell lines, it is easy to detect Arthritis Rheum. 40, 627–638. virus particles by electron microscopy or viral transcripts by Northern blots (Figure 1) although the level of expres-† To whom correspondence should be addressed. Present address: …