Bolger G, Lapeyre N, Rhéaume M, Kibler P, Bousquet C, Garneau M, Cordingley M
Department of Biological Sciences, Boehringer Ingelheim (Canada) Limited, Laval, Quebec, Canada.
Antiviral Res. 1999 Dec 31;44(3):155-65. doi: 10.1016/s0166-3542(99)00063-7.
Acute intraperitoneal infection of weanling BALB/c mice with murine cytomegalovirus (MCMV) resulted in an inoculum titer-dependent weight loss, mortality and elevation of plasma transaminases (ALT: alanine transaminase and AST: aspartate transaminase). Three days post infection (p.i.) with 10(4.85) plaque forming units (pfu) there was 90% mortality with a mean death day p.i. of 4.1 +/- 0.2. Plasma levels of ALT and AST were elevated 24- and 15-fold, respectively. Organ titers of virus (log10 pfu/g tissue) were 6.16 in the liver, 6.05 in the spleen, 4.0-4.7 in the lung, heart, kidney and intestine and undetectable in the muscle and brain. Organ concentrations (units/g wet-weight) of ALT were highest in the liver, whilst for AST the highest levels were found in the heart. The concentrations of ALT but not AST were reduced (35-55%) in the infected liver; the concentrations of ALT and AST were not changed in other infected organs. There were excellent correlations (r > 0.95) between viral titers in the liver, increases of plasma ALT and depletion of liver ALT. HPMPC and ganciclovir administered either p.o. or s.c. reduced mortality, increases in plasma transaminases and viral burdens in the liver and prevented depletion of liver ALT. HPMPC was approximately 10-fold more potent than ganciclovir. These results strongly suggest that intraperitoneal infection of the BALB/c mouse with MCMV represents an animal model of CMV hepatitis that can be monitored by measuring plasma ALT.
用鼠巨细胞病毒（MCMV）对断奶的BALB/c小鼠进行急性腹腔感染，会导致接种物滴度依赖性体重减轻、死亡率升高以及血浆转氨酶（ALT：丙氨酸转氨酶和AST：天冬氨酸转氨酶）升高。感染10(4.85) 个空斑形成单位（pfu）后3天（p.i.），死亡率达90%，平均死亡日为感染后4.1±0.2天。血浆中ALT和AST水平分别升高了24倍和15倍。病毒在各器官中的滴度（log10 pfu/g组织）：肝脏为6.16，脾脏为6.05，肺、心脏、肾脏和肠道为4.0 - 4.7，肌肉和大脑中未检测到。ALT的器官浓度（单位/g湿重）在肝脏中最高，而AST的最高水平则在心脏中。感染的肝脏中ALT浓度降低（35 - 55%），但AST浓度未变；其他感染器官中ALT和AST的浓度未改变。肝脏中的病毒滴度、血浆ALT升高以及肝脏ALT消耗之间存在极好的相关性（r > 0.95）。口服或皮下注射HPMPC和更昔洛韦可降低死亡率、血浆转氨酶升高以及肝脏中的病毒载量，并防止肝脏ALT消耗。HPMPC的效力比更昔洛韦强约10倍。这些结果强烈表明，用MCMV对BALB/c小鼠进行腹腔感染代表了一种可通过测量血浆ALT进行监测的CMV肝炎动物模型。
