Aquino-de Jesus M J, Griffith B P
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06510.
Antiviral Res. 1989 Nov;12(4):181-93. doi: 10.1016/0166-3542(89)90028-4.
An experimental model for testing antiviral agents against severe cytomegalovirus (CMV) infection in immunocompromised hosts was developed. The model consisted of cyclophosphamide (Cy) treatment of CMV-infected guinea pigs to simulate CMV infection in immunodeficient individuals. Of the 3 Cy regimens tested, a single 300 mg/kg dose administered one day after virus inoculation resulted in the most severe CMV infection considering mortality rates, mean day of death and loss of body weight. Evaluation of responses to both T and B cell mitogens suggested that the severe and lethal CMV infection resulted from the combined immunosuppressive effect of Cy and CMV. The nucleoside analog [9-(1-3-dihydroxy-2-propoxymethyl)guanine (DHPG) was used to assess the usefulness of the CMV-infected immunocompromised host model. DHPG (100 mg/kg/day for 8 days) prevented death but did not reduce virus infectivity titers in blood of Cy-treated, CMV-infected guinea pigs. This model of CMV infection in immunocompromised guinea pig is a relevant and convenient experimental tool for the assessment of candidate anti-CMV agents under well-defined experimental conditions, such as appropriate CMV inoculum and Cy regimen.
建立了一种用于测试抗病毒药物对免疫功能低下宿主严重巨细胞病毒（CMV）感染疗效的实验模型。该模型包括用环磷酰胺（Cy）处理CMV感染的豚鼠，以模拟免疫缺陷个体中的CMV感染。在所测试的3种Cy方案中，在病毒接种后一天给予单次300mg/kg剂量，从死亡率、平均死亡天数和体重减轻情况来看，导致了最严重的CMV感染。对T细胞和B细胞有丝分裂原反应的评估表明，严重且致命的CMV感染是由Cy和CMV的联合免疫抑制作用所致。核苷类似物[9-(1-3-二羟基-2-丙氧基甲基)鸟嘌呤（DHPG）]被用于评估CMV感染的免疫功能低下宿主模型的效用。DHPG（100mg/kg/天，共8天）可预防死亡，但并未降低经Cy处理的CMV感染豚鼠血液中的病毒感染滴度。这种免疫功能低下豚鼠的CMV感染模型是一种相关且便捷的实验工具，可在明确的实验条件下（如合适的CMV接种物和Cy方案）评估候选抗CMV药物。
