Awan A R, Harmenberg J, Kristofferson A, Field H J
Centre for Veterinary Science, University of Cambridge, UK.
Antiviral Res. 1998 Apr;38(1):43-53. doi: 10.1016/s0166-3542(98)00003-5.
Existing murine models for cutaneous herpes simplex virus type 1 (HSV-1) infection have limited relevance to recurrent disease in humans, since the infection is usually primary rather than reactivated and infection occurs in the absence of an established immune response. To obtain a reproducible model to study the effects of topical antiviral therapy on recurrent disease we have adapted a mouse model which employs zosteriform spread of HSV-1 in the presence of adoptive transfer of immunity (ATI) which mimics human recrudescent lesions. Mice were infected with HSV-1 by scarification at the lateroventral line of the neck; 2 days later, the mice received adoptive transfer of immune cells from the cervical lymph nodes of syngeneic mice that had been infected in the ear pinna with the same strain of virus 7 days earlier. ATI resulted in a heightened inflammatory response in the target tissues for virus replication. Virus was cleared more quickly from the infected tissues in comparison with mice similarly inoculated without ATI, however, the intensity and duration of the inflammation was greater. The model was then used to test the effect of a topical formulation of foscarnet. The results presented demonstrate that the ATI model can provide useful data concerning the efficacy of topical antiviral chemotherapy in man.
现有的1型单纯疱疹病毒(HSV-1)皮肤感染小鼠模型与人类复发性疾病的相关性有限,因为该感染通常是原发性的而非再激活的,并且感染发生时不存在已建立的免疫反应。为了获得一个可重复的模型来研究局部抗病毒治疗对复发性疾病的影响,我们采用了一种小鼠模型,该模型利用在免疫过继转移(ATI)存在的情况下HSV-1的带状扩散,模拟人类复发病变。通过在颈部腹侧线划痕将HSV-1感染小鼠;2天后,这些小鼠接受来自同基因小鼠颈部淋巴结免疫细胞的过继转移,这些同基因小鼠7天前在耳廓用相同病毒株感染过。ATI导致病毒复制的靶组织中炎症反应增强。与未进行ATI的类似接种小鼠相比,病毒从感染组织中清除得更快,然而,炎症的强度和持续时间更大。然后使用该模型测试膦甲酸钠局部制剂的效果。给出的结果表明,ATI模型可以提供有关局部抗病毒化疗在人体中疗效的有用数据。