BACKGROUND: The human endogenous retrovirus K-18 (HERV-K18) encodes a superantigen that causes deregulation of the immune system. This provirus is transcriptionally silent, but can be induced by Epstein-Barr virus (EBV) infection and IFN-alpha treatment. OBJECTIVES: Since the herpesvirus EBV induces HERV-K18 expression in human B cells, it was of interest to determine if other herpesviruses would have similar HERV-K18 transactivation properties. Human herpesvirus (HHV)-6A, a neurotropic virus associated with multiple sclerosis, was a logical candidate for these studies. STUDY DESIGN: HSB2 cells (HHV-6-negative control), HSB2-ML cells (containing latent HHV-6A genome) and HSB2/HHV-6A cells (HSB-2 cells productively infected with HHV-6A) were compared for their level of HERV-K18 transcription, using quantitative RT-PCR. RESULTS: Latently infected HSB2-ML cells showed a significant increase in HERV-K18 RNA compared to the control cells. HERV-K18 expression was even greater in HSB2 cells productively infected with HHV-6A for 78h. CONCLUSION: These results imply that HHV-6A, either in latent form or during acute infection, directly transactivates HERV-K18. This HERV-K18 induction may be mediated through IFN-alpha that is produced by the HHV-6A-infected cells. The functional implications of superantigen expression are discussed.
BACKGROUND: The human endogenous retrovirus K-18 (HERV-K18) encodes a superantigen that causes deregulation of the immune system. This provirus is transcriptionally silent, but can be induced by Epstein-Barr virus (EBV) infection and IFN-alpha treatment. OBJECTIVES: Since the herpesvirusEBV induces HERV-K18 expression in human B cells, it was of interest to determine if other herpesviruses would have similar HERV-K18 transactivation properties. Humanherpesvirus (HHV)-6A, a neurotropic virus associated with multiple sclerosis, was a logical candidate for these studies. STUDY DESIGN: HSB2 cells (HHV-6-negative control), HSB2-ML cells (containing latent HHV-6A genome) and HSB2/HHV-6A cells (HSB-2 cells productively infected with HHV-6A) were compared for their level of HERV-K18 transcription, using quantitative RT-PCR. RESULTS:Latently infected HSB2-ML cells showed a significant increase in HERV-K18 RNA compared to the control cells. HERV-K18 expression was even greater in HSB2 cells productively infected with HHV-6A for 78h. CONCLUSION: These results imply that HHV-6A, either in latent form or during acute infection, directly transactivates HERV-K18. This HERV-K18 induction may be mediated through IFN-alpha that is produced by the HHV-6A-infected cells. The functional implications of superantigen expression are discussed.
Authors: Marta J Gonzalez-Hernandez; Michael D Swanson; Rafael Contreras-Galindo; Sarah Cookinham; Steven R King; Richard J Noel; Mark H Kaplan; David M Markovitz Journal: J Virol Date: 2012-05-16 Impact factor: 5.103
Authors: Kenny L De Meirleir; Svetlana F Khaiboullina; Marc Frémont; Jan Hulstaert; Albert A Rizvanov; András Palotás; Vincent C Lombardi Journal: In Vivo Date: 2013 Mar-Apr Impact factor: 2.155
Authors: Marta J Gonzalez-Hernandez; James D Cavalcoli; Maureen A Sartor; Rafael Contreras-Galindo; Fan Meng; Manhong Dai; Derek Dube; Anjan K Saha; Scott D Gitlin; Gilbert S Omenn; Mark H Kaplan; David M Markovitz Journal: J Virol Date: 2014-05-28 Impact factor: 5.103