Ampligen inhibits human herpesvirus-6 in vitro.
The recently discovered human herpesvirus-6 (HHV-6) is being associated with an increasing number of conditions in which there is evidence of immunologic dysfunction. A number of widely available antiviral agents have shown little or no activity against the virus. We found that Ampligen [Poly (1): Poly (C12U), a synthetic, mismatched, double-stranded RNA, has potent, previously unexpected antiviral effects. Cells known to allow replication of HHV-6 were infected with the virus and treated with Ampligen under various conditions. When cells were pretreated with Ampligen (concentrations of 100 or 200 micrograms/ml) prior to infection or treated shortly after infection, viral replication was inhibited by 46-98%. At 100 and 200 micrograms/ml, Ampligen also inhibited the DNA polymerase activity of HHV-6 by 42-98%. When lower concentrations of Ampligen (10 and 50 micrograms/ml) were used, only pretreatment of cells, with Ampligen, followed by virus infection and carrying the infected cells with Ampligen, significantly inhibited HHV-6 infection (83.7 and 89.1% respectively). Indirect evidence suggests that Ampligen may inhibit viral attachment to cellular receptors and/or inhibit intracellular maturation of the virus. The above concentrations of Ampligen were not toxic to the cells used in the study. Given these in vitro findings, and the low frequency of toxicity reported with the use of Ampligen, clinical trials of this drug in patients with evidence of reactivated HHV-6 infection would seem to be warranted.
Ablashi
D V
DV
National Cancer Institute, Bethesda, MD 20892.
Berneman
Z N
ZN
Williams
M
M
Strayer
D R
DR
Kramarsky
B
B
Suhadolnik
R J
RJ
Reichenbach
N
N
Hiltzges
P
P
Komaroff
A L
AL
D000956:Antigens, Viral / Q000096:biosynthesis; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003470:Culture Media; D015654:Herpesvirus 6, Human / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors; D011070:Poly I-C / Q000494:pharmacology*; D011072:Poly U / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000494:pharmacology; D013601:T-Lymphocytes / Q000821:virology; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects*
D000956:Antigens, Viral; D000998:Antiviral Agents; D003470:Culture Media; D019384:Nucleic Acid Synthesis Inhibitors; D012330:RNA, Double-Stranded; D011072:Poly U; C047490:poly(I).poly(c12,U); D011070:Poly I-C