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.
Mishin
Vasiliy P
VP
Department of Internal Medicine, University of Virginia Health Sciences System, Charlottesville, USA.
Hayden
Frederick G
FG
Signorelli
Kathy L
KL
Gubareva
Larisa V
LV
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