3-Deazaneplanocin A induces massively increased interferon-α production in Ebola virus-infected mice

Mike Bray, Jo Lynne Raymond, Thomas Geisbert, Robert O. Baker

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

3-Deazaneplanocin A, an analog of adenosine, is a potent inhibitor of Ebola virus replication. A single dose early in infection prevents illness and death in Ebola virus-infected mice. The ability of this and similar compounds to block both RNA and DNA viruses has been attributed to the inhibition of a cellular enzyme, S-adenosylhomocysteine hydrolase (SAH), indirectly resulting in reduced methylation of the 5′ cap of viral messenger RNA. However, we found that the protective effect of the drug resulted from massively increased production of interferon-α in Ebola-infected, but not uninfected mice. Peak interferon levels increased with the extent of disease at the time of treatment, indicating that production was boosted only in virus-infected cells. Ebola virus has been shown to suppress innate antiviral mechanisms of the type I interferon response. 3-Deazaneplanocin A appears to reverse such suppression, restricting viral dissemination. Further development should focus on identifying adenosine analogues that produce a similar effect in Ebola virus-infected primates.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalAntiviral Research
Volume55
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Ebolavirus
Interferons
Adenosine
Adenosylhomocysteinase
Protective Agents
Interferon Type I
DNA Viruses
RNA Viruses
Viral RNA
Virus Replication
Methylation
Primates
Antiviral Agents
Viruses
Messenger RNA
3-deazaneplanocin
Enzymes
Infection

Keywords

  • Antiviral therapy
  • Ebola virus
  • Filovirus
  • Interferon-alpha
  • S-Adenosyl-L-homocysteine hydrolase

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

3-Deazaneplanocin A induces massively increased interferon-α production in Ebola virus-infected mice. / Bray, Mike; Raymond, Jo Lynne; Geisbert, Thomas; Baker, Robert O.

In: Antiviral Research, Vol. 55, No. 1, 2002, p. 151-159.

Research output: Contribution to journalArticle

Bray, Mike ; Raymond, Jo Lynne ; Geisbert, Thomas ; Baker, Robert O. / 3-Deazaneplanocin A induces massively increased interferon-α production in Ebola virus-infected mice. In: Antiviral Research. 2002 ; Vol. 55, No. 1. pp. 151-159.
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