Poly(I) *  Poly(C12U) Inhibits In Vitro Replication of Human Herpesvirus Type 6.

Poly(I) *  poly(C12U) (Ampligen; HEM Pharmaceuticals, Rockville, MD) is an antiviral drug that has been used to treat human immunodeficiency virus (HIV)-positive patients with AIDS-related complex or AIDS. More recently, Ampligen was also used in vivo to treat a limited number patients with chronic fatigue syndrome (CFS) whose peripheral blood lymphocytes were positive for human herpesvirus type 6 (HHV-6) antigens. Studies have shown that HHV-6 is highly reactivated in patients with CFS. Since the specificity of Ampligen’s activity against HHV-6 infection has never been tested directly, we were interested in evaluating the drug in vitro as an anti-HHV-6 agent. HSB-2 cells (immature T lymphocytes) were infected with HHV-6 (variant A, GS strain). One thousand TCID„of HHV-6 and four dosages of Ampligen (10, 50, l00, and 200 pg/mL) were used in this study. HHV-6 infection was monitored by observation of morphological changes in cells, by detection o HHV-6 antigens by polyclonal and monoclonal antibodies t< HHV-6, and by electron microscopy.

Ampligen was most effective in blocking HHV-6 infectior (98% inhibition) at the 100- and 200-ug doses (these doses wen not toxic to HSB-2 cells) ashen the cells were pretreated with th< drug prior to viral infection and maintained in the presence o the drug. Ampligen also inhibited HHV-6 infection (>95%) when the cells were first infected with HHV-6 and then treater with the drug; HHV-6 infection was blocked (95% inhibition) when virus and drug were added together to the HSB-2 cells. When the Ampligen was removed from the virus-infected cell culture, the HHV-6 infection reappeared slowly but never reached the same level as that observed in only virus-infected cells (55% vs. 95%). Ampligen also significantly (>98%) inhibited HHV-6 DNA polymerase activity. Electron micrographs showed either unassembled virus in the nucleus or extracellular virus particles, which could not enter the cell. This finding suggests that Ampligen may block the receptors on the cell surface, which prevents virus entry and adsorption to the cell.

The data show that Ampligen is a potent inhibitor of HHV-6 vephcation. The mechanism of action of Ampligen is still to be investigated.

Reprints or correspondence: Dr. Dharam V. Ablashi, 4117 Barnsley Lane, Olney, Maryland 20832.

Clinical Infectious Diseases 1994;18(Supp' I):S113

Keywords: hhv6 ampligen infection treatment virus albalshi