Evaluation of methyl inosine monophosphate (MIMP) and peramivir activities in a murine model of lethal influenza A virus infection.
Evaluation of methyl inosine monophosphate (MIMP) and peramivir activities in a murine model of lethal influenza A virus infection.
复制标题
甲基肌苷单磷酸 (MIMP) 和帕拉米韦在致死性甲型流感病毒感染小鼠模型中的活性评估。
DOI：
10.1016/j.antiviral.2006.02.006
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发表时间：
2006
影响因子：
7.6
通讯作者：
Gubareva,LarisaV
中科院分区：
文献类型：
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作者：
Mishin,VasiliyP;Hayden,FrederickG;Signorelli,KathyL;Gubareva,LarisaV
利用近交系小鼠模型（BALB/c）评估免疫调节剂甲基肌苷5′-单磷酸（MIMP）对甲型流感病毒/PR/8/34（H1N1）感染的保护作用。与感染雾化病毒的远系繁殖小鼠（NMRI）报告的数据相反（Masihi，Hadden，2003. J. Int. Immunopharmacol. 3，1205-1215），在攻击前1天鼻内和/或攻击后口服MIMP处理5天（高达10 mg/kg/天）的近交系动物中，感染结果没有改善。尽管如此，通过在攻毒后每天一次给予神经氨酸酶抑制剂帕拉米韦（10 mg/kg/天）持续5天，可提供完全的致死保护。我们推测，在近交系小鼠中由鼻内攻击引起的疾病的快速进展可能使MIP治疗无效。我们的研究结果强调，需要仔细考虑小鼠株和病毒的攻击路线，在设计实验利用致命的流感病毒感染。
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 10mg/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 (10mg/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.