Evaluation of methyl inosine monophosphate (MIMP) and peramivir activities in a murine model of lethal influenza A virus infection.
An inbred murine model (BALB/c) was utilized to assess the protective effect of the immunomodulator methyl inosine 5'-monophosphate (MIMP) against infection with influenza A/PR/8/34 (H1N1) virus. Contrary to the data reported for outbred mice (NMRI) infected with the aerosolized virus (Masihi, Hadden, 2003. J. Int. Immunopharmacol. 3, 1205-1215), there were no improvements in the outcomes of infection in the inbred animals treated with MIMP intranasally 1 day before the challenge and/or orally after the challenge for 5 days (up to 10 mg/kg/day). Nevertheless, complete protection against lethality was afforded by the treatment with the neuraminidase inhibitor peramivir given once daily for 5 days after the challenge (10 mg/kg/day). We speculate that the rapid progression of the disease in inbred mice caused by the intranasal challenge may render the MIMP-treatment ineffective. Our results emphasize the need for careful consideration of murine strains and routes of virus challenge in the design of experiments utilizing lethal influenza virus infection.
Department of Internal Medicine, University of Virginia Health Sciences System, Charlottesville, USA.
Vasiliy P
VP
Mishin
Frederick G
FG
Hayden
Kathy L
KL
Signorelli
Larisa V
LV
Gubareva
D000146:Acids, Carbocyclic; D000367:Age Factors; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001835:Body Weight; D003517:Cyclopentanes / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000254:growth & development*; D007291:Inosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000821:virology*
D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; D007291:Inosine Monophosphate; C076557:methyl inosine monophosphate; C414210:peramivir