Adenosine dialdehyde: a potent inhibitor of vaccinia virus multiplication in mouse L929 cells.

Abstract

Adenosine dialdehyde (2'-O-[(R)-formyl(adenin-9-yl)methyl]-(R)-glyceraldehyde), formed by periodate oxidation of adenosine, is a potent inhibitor of S-adenosylhomocysteine hydrolase (EC 3.3.1.1.) in mouse L929 cells. Consequently, the dialdehyde produces an increase in intracellular levels of S-adenosylhomocysteine and subsequent inhibition of S-adenosylmethionine-dependent macromolecular methylations. In the present study we show that adenosine dialdehyde is also a potent inhibitor of vaccinia virus plaque formation in monolayer cultures of L cells. When added to the culture medium immediately following attachment of the virus, concentrations of the dialdehyde as low as 0.5 microM produce greater than 90% inhibition of plaque formation after 72 hr. The efficacy of the compound is greatest when added within 8 hr of virus attachment and gradually decreases in a time-dependent manner when added after this point. Treatment of L cells with 5 microM adenosine dialdehyde for 60 min prior to virus infection causes a transient, but virtually complete loss of S-adenosylhomocysteine hydrolase activity and subsequent 3-fold increase in the intracellular S-adenosylhomocysteine/S-adenosylmethionine ratio. Continuous exposure of infected cells to the dialdehyde results in prolonged inhibition of S-adenosylhomocysteine hydrolase accompanied by a 10-fold increase in the S-adenosylhomocysteine/S-adenosylmethionine ratio. Associated with these changes in the dialdehyde-treated, infected cells are an inhibition of early virus-specific protein synthesis and a 13% decrease in methylation of the cytoplasmic poly A+-mRNA. The antiviral action of this compound thus appears to be related to a decrease in viral mRNA methylation (e.g., the 5'-terminal cap structure) which results in suppressed translation of viral proteins essential for virus replication.

• Authors: B T Keller, R T Borchardt
• Journal: Molecular pharmacology (Mol Pharmacol) Vol. 31 Issue 5 Pg. 485-92 (May 1987) ISSN: 0026-895X [Print] United States
• PMID: 3574293 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antiviral Agents
• RNA, Messenger
• RNA, Viral
• Viral Proteins
• periodate-oxidized adenosine
• Hydrolases
• Adenosylhomocysteinase
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Adenosylhomocysteinase
• Animals
• Antiviral Agents
• Hydrolases (antagonists & inhibitors)
• L Cells
• Methylation
• Mice
• RNA, Messenger (metabolism)
• RNA, Viral (metabolism)
• Vaccinia virus (drug effects, growth & development)
• Viral Proteins (biosynthesis)
• Virus Replication (drug effects)