Human endogenous retrovirus HERV-K(HML-2) Rec expression and transcriptional activities in normal and rheumatoid arthritis synovia

Abstract

Objective: Despite abundance in the genome, the possible functions of human endogenous retrovirus (HERV) sequences are not well understood. The involvement of HERV in various disease conditions, such as germ cell tumors or autoimmune diseases like rheumatoid arthritis (RA), has been suggested. We investigated expression of HERV-K(HML-2) env-derived transcripts in normal and RA synovia.

Methods: We analyzed HERV-K(HML-2) expression on the mRNA and protein level by RT-PCR analysis and immunofluorescence labeling of the HERV-K(HML-2) Rec (formerly cORF) protein. We examined synovial cell cultures from normal synovia (n = 9), from patients with RA (n = 26), and osteoarthritis (OA, n = 4), and uncultured synovial tissues (RA, n = 12; normal synovia, n = 1).

Results: HERV-K Rec protein was expressed in all normal synovial specimens, and in the majority of RA and OA cases. We demonstrate for the first time expression of HERV-K protein in synovial tissue. RT-PCR and sequence analysis of cloned RT-PCR products confirmed expression of spliced HERV-K(HML-2) env transcripts in normal and in arthritic synovia. In addition to rec mRNA, several alternatively spliced transcripts, including np9, were identified. However, different amounts of the various RT-PCR products indicate different expression levels of HERV-K(HML-2) env-derived transcripts in RA compared to normal synovia, with apparently lower expression levels in arthritic synovia.

Conclusion: These findings imply a physiological role of HERV-K(HML-2) Rec in synovial tissue. Differences in the expression of HERV-K env-derived transcripts in RA synovia may be caused by disease-specific changes in the general expression pattern.