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小鼠卡拉帕鲁布尼亚病毒肝脏感染及免疫调节剂介导的抗病毒保护作用的特征分析

Characterization of murine Caraparu Bunyavirus liver infection and immunomodulator-mediated antiviral protection.

作者信息

Brinton M A, Gavin E I, Lo W K, Pinto A J, Morahan P S

机构信息

Wistar Institute, Philadelphia, PA 19104.

出版信息

Antiviral Res. 1993 Feb;20(2):155-71. doi: 10.1016/0166-3542(93)90005-4.

Abstract

A rapid, peripheral disease model utilizing the Bunyavirus, Caraparu, was established in mice for the evaluation of antiviral therapy with immunomodulators. 4-6-week-old B6C3F1 female mice, inoculated intraperitoneally with virus, developed coagulative liver necrosis and died between 4-6 days after infection. This Caraparu disease model was relatively resistant to treatment with immunomodulators, such as ABMP, Ampligen, alpha-interferon (IFN-alpha) or beta-interferon (IFN-beta). However, a significant increase in median survival time (MST) was consistently observed upon treatment with gamma-interferon (IFN-gamma). The nucleoside analog--ribavirin--was highly effective against Caraparu virus in repeated treatment schedules begun on either day -1, day 0, or day +1 of infection. Ribavirin gave little protection when initiation of treatment was delayed until day +2. However, combined treatment with IFN-gamma, starting on day 0 and ribavirin starting on day +2, significantly reduced mortality.

摘要

利用布尼亚病毒卡拉帕鲁建立了一种快速的外周疾病模型,用于在小鼠中评估免疫调节剂的抗病毒治疗效果。4至6周龄的B6C3F1雌性小鼠经腹腔接种病毒后,会出现凝固性肝坏死,并在感染后4至6天内死亡。这种卡拉帕鲁疾病模型对免疫调节剂如ABMP、 Ampligen、α干扰素(IFN-α)或β干扰素(IFN-β)的治疗相对耐药。然而,用γ干扰素(IFN-γ)治疗时,始终观察到中位生存时间(MST)显著增加。核苷类似物利巴韦林在感染第-1天、第0天或第+1天开始的重复治疗方案中对卡拉帕鲁病毒高度有效。当治疗开始推迟到第+2天时,利巴韦林几乎没有保护作用。然而,从第0天开始用IFN-γ和从第+2天开始用利巴韦林联合治疗,可显著降低死亡率。

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