HHV-6A infection induces expression of HERV-K18-encoded superantigen.
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.


OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Tai
Albert K
AK
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, United States.
Luka
Janos
J
Ablashi
Dharam
D
Huber
Brigitte T
BT
D002460:Cell Line; D020077:Endogenous Retroviruses / Q000502:physiology*; D020869:Gene Expression Profiling; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018089:Superantigens / Q000096:biosynthesis* / Q000235:genetics
C107453:ERVK-18 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D018089:Superantigens