Efficacy of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine for the treatment of lethal vaccinia virus infections in severe combined immune deficiency (SCID) mice

J Med Virol. 1993 Nov;41(3):242-6. doi: 10.1002/jmv.1890410312.


Severe combined immune deficient (SCID) mice inoculated intravenously with vaccinia virus (VV) became sick within 6-8 days and died 10-12 days after infection. Tail lesions developed and the number depended on the virus inoculum. Age-matched immunocompetent NMRI mice similarly infected also developed tail lesions but did not become sick. When the infected SCID mice were treated with the acyclic nucleoside phosphonate HPMPC [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine], either for 5 consecutive days starting on the day of infection or for 5 consecutive days starting on day 2, 4, or 6 post infection, or as a single dose at 7 days or 1 day before infection, VV-associated death was significantly delayed. VV-infected SCID mice that received two doses of 20 mg/kg of HPMPC every week survived the infection for about 130 days. The period during which the mice remained disease-free following HPMPC treatment correlated with the absence of detectable virus in their organs. The VV/SCID mouse model employed here may be useful for determining whether (attenuated) recombinant VV (carrying HIV genes) may have detrimental effects in the immunodeficient host. HPMPC may be considered as a drug candidate for the treatment and prophylaxis of such complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Brain / microbiology
  • Cidofovir
  • Cytosine / analogs & derivatives*
  • Cytosine / pharmacology
  • Cytosine / therapeutic use
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Kidney / microbiology
  • Liver / microbiology
  • Lung / microbiology
  • Mice
  • Mice, SCID
  • Organophosphonates*
  • Organophosphorus Compounds / pharmacology
  • Organophosphorus Compounds / therapeutic use*
  • Vaccinia / complications
  • Vaccinia / drug therapy*
  • Vaccinia / microbiology
  • Vaccinia virus / drug effects*
  • Vaccinia virus / physiology
  • Virus Replication / drug effects


  • Antiviral Agents
  • Organophosphonates
  • Organophosphorus Compounds
  • Cytosine
  • Cidofovir