Effect of (r)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (H2G) and AZT-lipid-PFA on human herpesvirus-6B infected cells.
BACKGROUND
Human herpesvirus-6 (HHV-6) has been associated with a wide spectrum of diseases. (r)-9-[4-Hydroxy-2-(hydroxymethyl)butyl]guanine (H2G) is an acyclic guanosine analogue that is structurally similar to acyclovir and is in clinical development for treatment of herpesvirus infections. H2G has been found to have activity against HSV type 1, HSV type 2, and HHV-6 in lymphoblast cell lines. A new anti-viral duplex drug, 3'-azido-3'-deoxythymidylyl-(5'-->2-O)-3-O-octadecyl-sn-glycerol (AZT-lipid-PFA), linking zidovudine (AZT) and foscarnet (PFA) via a lipophilic octadecylglycerol residue (lipid) also exhibits anti-viral activities against HIV, HSV type 1 and HCMV.


OBJECTIVE
To assess the efficacy of H2G and AZT-lipid-PFA conjugate against HHV-6.


METHODS
Drug-associated toxicity and proliferative response were evaluated. We conducted in vitro experiments to determine the efficacy of H2G and an AZT-lipid-PFA conjugate in interfering with expression HHV-6 viral transcript in primary human peripheral blood mononuclear cells (PBMC).


RESULTS
Both H2G and AZT-lipid-PFA were effective at inhibiting expression of HHV-6 gene transcript at comparable concentrations. Additionally, while AZT-lipid-PFA treatment was toxic to cells at concentrations above 5microM, H2G treatment was associated with minimal cytotoxicity.


CONCLUSIONS
These data suggest the potential application of these anti-viral compounds in controlling HHV-6 infection.
Yao
Karen
K
Viral Immunology Section, Neuroimmunology Branch, NINDS, NIH, Bethesda, MD 20892, United States.
Hoest
Christel
C
Rashti
Farzin
F
Schott
Timm C
TC
Jacobson
Steven
S
D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D022781:Hepatocytes / Q000821:virology; D015654:Herpesvirus 6, Human / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008826:Microbial Sensitivity Tests / Q000379:methods; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity
D000998:Antiviral Agents; C051755:9-(4-hydroxy-2-(hydroxymethyl)butyl)guanine; D015215:Zidovudine; D006147:Guanine