Martin J R, Reed E V
Laboratory of Experimental Neuropathology, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892.
Microb Pathog. 1986 Apr;1(2):181-9. doi: 10.1016/0882-4010(86)90020-3.
To establish a reactivation model of genital and central nervous system infection, 3- to 12-week-old outbred or BALB/c mice were inoculated vaginally with the HG-52 strain of herpes simplex virus type 2 (HSV-2). Primary infection was confirmed by serially positive vaginal cultures. Mortality in 6- and 12-week old infected mice was about 20%. In survivors, clearance of infectious virus was confirmed in serially negative vaginal cultures. At 6 weeks, immunosuppression of survivors with cyclophosphamide and antilymphocyte serum was begun. Recurrent virus shedding, monitored by daily vaginal cultures, was detected in the majority of animals. All mice became moribund or died, usually during the third to fifth weeks of immunosuppression. Brains and spinal cords from which all sensory ganglia had been removed were homogenized and inoculated onto cultures. One or both central nervous system (CNS) samples were virus-positive in nearly half of these mice, and cell-free virus was isolated from most positive brain and cord supernatants tested. Three-fourths of mice had evidence of virus reactivation with immunosuppression, as indicated by vaginal or CNS isolations, and by failure to isolate virus by identical means in matched infected, non-immunosuppressed controls. Vaginal, spinal cord and brain isolates occurred independently of one another in many immunosuppressed mice, and could not be predicted from presence or absence of external genital lesions during primary infection. These experiments show that with immunosuppression, reactivations of latent HSV-2 infections in mice can be detected in the genital tract and CNS, and provide a model to study productive, recurrent CNS infection and disease.
为建立生殖器和中枢神经系统感染的再激活模型，将3至12周龄的远交群或BALB/c小鼠经阴道接种2型单纯疱疹病毒（HSV-2）HG-52株。通过连续阴道培养呈阳性来确认原发性感染。6周龄和12周龄感染小鼠的死亡率约为20%。在存活小鼠中，连续阴道培养呈阴性可确认感染性病毒已清除。6周时，开始用环磷酰胺和抗淋巴细胞血清对存活小鼠进行免疫抑制。通过每日阴道培养监测，大多数动物检测到复发性病毒脱落。所有小鼠通常在免疫抑制的第三至第五周变得濒死或死亡。将已切除所有感觉神经节的脑和脊髓匀浆并接种到培养物上。在近一半的这些小鼠中，一个或两个中枢神经系统（CNS）样本呈病毒阳性，并且从大多数检测的阳性脑和脊髓上清液中分离出无细胞病毒。四分之三的小鼠有免疫抑制导致病毒再激活的证据，这通过阴道或中枢神经系统分离以及在匹配的感染、未免疫抑制对照中用相同方法未能分离出病毒来表明。在许多免疫抑制小鼠中，阴道、脊髓和脑的病毒分离彼此独立发生，并且不能根据原发性感染期间外生殖器病变的有无来预测。这些实验表明，通过免疫抑制，可以在小鼠的生殖道和中枢神经系统中检测到潜伏性HSV-2感染的再激活，并提供了一个研究有活性的、复发性中枢神经系统感染和疾病的模型。
