EFFICACY OF (S)-1-(3-HYDROXY-2-PHOSPHONYLMETHOXYPROPYL)CYTOSINE FOR THE TREATMENT OF LETHAL VACCINIA VIRUS-INFECTIONS IN SEVERE COMBINED IMMUNE-DEFICIENCY (SCID) MICE
EFFICACY OF (S)-1-(3-HYDROXY-2-PHOSPHONYLMETHOXYPROPYL)CYTOSINE FOR THE TREATMENT OF LETHAL VACCINIA VIRUS-INFECTIONS IN SEVERE COMBINED IMMUNE-DEFICIENCY (SCID) MICE
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DOI：
10.1002/jmv.1890410312
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发表时间：
1993-11-01
影响因子：
12.7
通讯作者：
DECLERCQ, E
中科院分区：
文献类型：
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作者：
NEYTS, J;DECLERCQ, E
经静脉注射牛痘病毒（VV）的严重联合免疫缺陷（SCID）小鼠在感染后6-8天发病，10-12天死亡。出现尾损，数量与病毒接种量有关。同样被感染的年龄匹配的免疫能力的NMRI小鼠也出现了尾巴病变，但没有生病。当感染SCID小鼠用无环核苷膦酸hmpc [(S)-1-（3-羟基-2-膦基甲氧基丙基）胞嘧啶]治疗时，无论是从感染当天开始连续5天，还是从感染后第2、4、6天开始连续5天，或在感染前7天或1天单次给药，vv相关死亡都明显延迟。感染vv的SCID小鼠每周接受两剂20 mg/kg的hmpc，感染后存活约130天。小鼠在接受hmpc治疗后保持无病状态的时间与器官中检测不到病毒相关。这里采用的VV/SCID小鼠模型可能有助于确定（减毒的）重组VV（携带HIV基因）是否可能对免疫缺陷宿主产生有害影响。hmpc可作为治疗和预防此类并发症的候选药物。(C) 1993 Wiley-Liss, Inc。
Severe combined immune deficient (SCID) mice inoculated intravenously with vaccinia virus (VV) became sick within 6-8 days and died 10-12 days after infection. Tail lesions developed and the number depended on the virus inoculum. Age-matched immunocompetent NMRI mice similarly infected also developed tail lesions but did not become sick. When the infected SCID mice were treated with the acyclic nucleoside phosphonate HPMPC [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine], either for 5 consecutive days starting on the day of infection or for 5 consecutive days starting on day 2, 4, or 6 post infection, or as a single dose at 7 days or 1 day before infection, VV-associated death was significantly delayed. VV-infected SCID mice that received two doses of 20 mg/kg of HPMPC every week survived the infection for about 130 days. The period during which the mice remained disease-free following HPMPC treatment correlated with the absence of detectable virus in their organs. The VV/SCID mouse model employed here may be useful for determining whether (attenuated) recombinant VV (carrying HIV genes) may have detrimental effects in the immunodeficient host. HPMPC may be considered as a drug candidate for the treatment and prophylaxis of such complications. (C) 1993 Wiley-Liss, Inc.