Kuehne R W, Pannier W L, Stephen E L
Antimicrob Agents Chemother. 1977 Apr;11(4):683-7. doi: 10.1128/AAC.11.4.683.
An indirect mouse model was utilized to evaluate the antiviral activity of several compounds against Venezuelan equine encephalomyelitis (VEE) virus infection in mice. Mice were given various dosages of lysine-stabilized polyriboinosinic acid-polyribocytidylic acid, a tilorone analogue, kethoxal, or mepacrine before and/or shortly after receiving one of several dose levels of attenuated strain TC-83 VEE virus. Twenty-one days later, the same mice were rechallenged intracranially with virulent Trinidad donkey strain VEE virus. Susceptibility to rechallenge was interpreted as evidence of drug effectiveness in completely preventing the initial immunizing virus infection. In contrast, if a drug lacked antiviral effectiveness, the initial attenuated infection stimulated sufficient immunity to protect mice against the virulent rechallenge. Both of the interferon inducers, lysine-stabilized polyriboinosinic acid-polyribocytidylic acid and tilorone analogue 11,567, possessed significant (P < 0.01) antiviral activity based upon this indirect model, whereas mepacrine and kethoxal were inactive. Results using the indirect method were confirmed by using the conventional direct method for evaluating the effectiveness of potentially useful antiviral compounds. The indirect mouse model described should prove useful for studying drug efficacy against certain viruses that are lethal only by intracranial inoculation.
利用间接小鼠模型评估几种化合物对小鼠委内瑞拉马脑炎（VEE）病毒感染的抗病毒活性。在接受几种剂量水平的减毒株TC - 83 VEE病毒之一之前和/或之后不久，给小鼠给予不同剂量的赖氨酸稳定化聚肌苷酸 - 聚胞苷酸、一种泰洛龙类似物、乙二醛或米帕林。21天后，用强毒特立尼达驴株VEE病毒对同一批小鼠进行颅内再攻击。对再攻击的易感性被解释为药物在完全预防初始免疫病毒感染方面有效性的证据。相反，如果一种药物缺乏抗病毒有效性，初始的减毒感染会刺激足够的免疫力来保护小鼠免受强毒再攻击感染。基于这种间接模型，两种干扰素诱导剂，赖氨酸稳定化聚肌苷酸 - 聚胞苷酸和泰洛龙类似物11,567，都具有显著（P < 0.01）的抗病毒活性，而米帕林和乙二醛则无活性。使用评估潜在有用抗病毒化合物有效性的传统直接方法证实了间接方法的结果。所描述的间接小鼠模型对于研究针对某些仅通过颅内接种致死的病毒的药物疗效应是有用的。
