Otani I, Fujii Y, Akari H, Mukai R, Mori K, Ono F, Kojima E, Machida M, Murakami K, Doi K, Yoshikawa Y
Tsukuba Primate Center, National Institute of Infectious Diseases, Ibaraki, Japan.
J Vet Med Sci. 1997 Oct;59(10):891-6. doi: 10.1292/jvms.59.891.
We studied the effects of 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG), an antiretroviral drug, in surface lymph nodes of rhesus monkeys (Macaca mulatta) chronically infected with simian immunodeficiency virus (SIV). The rhesus monkeys were treated with 25 mg/kg of 6-Cl-ddG every 8 hr for 2 weeks. We performed sequential biopsies of the surface lymph nodes three times: before, during, and after the drug treatment. The 6-Cl-ddG dramatically decreased the number of infectious virus (measured by limiting dilution assay) in lymph node mononuclear cells. This decrease was consistent with the decrease in the number of viral RNA-positive cells in lymph nodes (analyzed by in situ hybridization). Histopathological analysis revealed that hyperplastic lymphoid follicles were reduced in size, especially, enlarged areas of centroblasts in lymphoid follicles (the so-called dark areas of germinal centers) were declined. Our results demonstrated that 6-Cl-ddG decreased the viral burden concomitantly with reduced hyper-activation of germinal centers in lymphoid follicles of SIV-infected rhesus monkeys.
我们研究了抗逆转录病毒药物6-氯-2'，3'-双脱氧鸟苷（6-Cl-ddG）对慢性感染猿猴免疫缺陷病毒（SIV）的恒河猴（猕猴）浅表淋巴结的影响。恒河猴每8小时接受25mg/kg的6-Cl-ddG治疗，持续2周。我们在药物治疗前、治疗期间和治疗后对浅表淋巴结进行了三次连续活检。6-Cl-ddG显著降低了淋巴结单核细胞中感染性病毒的数量（通过有限稀释法测定）。这种减少与淋巴结中病毒RNA阳性细胞数量的减少一致（通过原位杂交分析）。组织病理学分析显示，增生性淋巴滤泡尺寸减小，尤其是淋巴滤泡中中心母细胞扩大区域（所谓生发中心的暗区）减少。我们的结果表明，6-Cl-ddG在降低SIV感染的恒河猴淋巴滤泡中生发中心过度激活的同时，降低了病毒载量。
