Human herpesvirus-6B induces expression of the human endogenous retrovirus K18-encoded superantigen

Background: The superantigen, encoded by the envelope gene (env) of the human endogenous retrovirus (HERV)-K18, may be involved in autoimmunity. Its expression is transactivated in B cells during infection with Epstein-Barr virus and in peripheral blood mononuclear cells (PBMCs) that are treated with IFN-alpha. Objectives: We investigated whether HHV-6B infection was able to induce the expression of HERV-K18 env. Study design: The expression of HERV-K18 env gene was measured by real-time quantitative PCR in HHV-6B-infected PBMC. Results: Infection of PBMCs with HHV-6B resulted in a rapid and dose-dependent induction of HERV-K18 env gene expression, predominantly in monocytes. Induction was dependent on the interaction of glycoprotein H with CD46, but did not require viral transcription or DNA synthesis. Cycloheximide inhibited both the induction and basal expression of HERV-K18 env, indicating that de novo synthesis of proteins was necessary. Conclusions: HHV-6B induced transcriptional activation of the endogenous superantigen HERV-K18 independently of virus replication, which may have consequences for the development of autoimmunity. (C) 2009 Elsevier B.V. All rights reserved.