单纯疱疹病毒Ⅱ型经不同途径感染BALB/c小鼠的病理学研究  

Pathogenesis of nasal and genital infection with herpes simplex virus type Ⅱ in BALB/c mice

作　　者：曾洁媛 李琦涵[2] 范胜涛[2] 廖芸[2] 冯敏[2] 徐兴丽[2] 沈冬[2] 王建斌[2] 程继帅 张莹 Zeng Jieyuan;Li Qihan;Fan Shengtao;Liao Yun;Feng Min;Xu Xingli;Shen Dong;Wang Jianbin;Chen Jishuai;Zhang Ying(Basic Medical College of Kunming Medical University, Kunming 650500, China;Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China)

机构地区：[1]昆明医科大学基础医学院,650500 [2]中国医学科学院&北京协和医学院医学生物学研究所,云南省重大传染病疫苗研发重点实验室,昆明650118

出　　处：《中华微生物学和免疫学杂志》2019年第7期485-491,共7页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金(31670173,81802868);中国医学科学院医学与健康科技创新工程项目(2016-I2M-1Q19);云南省重大科技专项(2017ZF020,2017ZFD06).

摘　　要：目的观察并比较分析单纯疱疹病毒Ⅱ型(herpes simplex virus type 2,HSV-2)经不同途径感染小鼠后的致病情况。方法将6周龄雌性BALB/c小鼠分为实验组和对照组。实验组小鼠分别经滴鼻、生殖道途径感染HSV-2(每只104CCID50/20 μl),对照组小鼠经上述两种途径注射PBS。感染后不同时间点,分别取肺、神经系统、生殖系统组织进行病理学观察及病毒载量检测。通过原位杂交对小鼠三叉和骶神经节中lat基因的表达进行定位,同时对组织中病毒进行重激活检测。结果两种途径感染HSV-2的小鼠体重在6 d后均呈下降趋势,且均能观察到组织病理损伤。鼻腔感染以肺泡壁充血、脑血管袖套、淋巴细胞浸润等肺部、中枢神经系统病理损伤为主;而生殖道感染组主要出现是骶神经节坏死、阴道和子宫嗜酸性粒细胞增多、卵巢充血等生殖道病理现象。经两种途径感染的小鼠组织器官中病毒载量的情况也印证了上述病理结果,即鼻腔感染组小鼠的神经、肺组织中病毒载量明显高于生殖道组,而生殖道感染组小鼠的生殖道和骶神经节中病毒增殖则明显高于鼻腔感染组。感染后28 d,在处于潜伏感染小鼠的三叉和骶神经节中均能检测到HSV-2 lat基因mRNA的阳性信号,并且采集的组织碎块均能在与Vero细胞共培养时使细胞病变,且生殖道感染组的lat基因阳性信号及重激活后病毒增殖趋势相对高于鼻腔感染组。结论HSV-2通过鼻腔和生殖道两种途径感染BALB/c小鼠均能引起组织病理损伤,且病理损伤空间特异性与感染途径密切相关。Objective To observe and analyze the pathological changes in BALB/c mice infected with herpes simplex virus typeⅡ(HSV-2) through nasal and genital inoculation. Methods Six-week old female BALB/c mice were divided into two groups, experimental and control groups. In the experimental group, the mice were infected with HSV-2 (104CCID50/20 μl per mouse) through nasal and genital tract inoculation. Accordingly, the mice in the control group were injected with equal volume of PBS. Tissue specimens were collected from lung, nervous system and reproductive system for pathological analysis and viral load detection at different time points after infection. Lat gene expression in mouse trigeminal and sacral ganglia was detected through in situ hybridization. In addition, the proliferation of viruses isolated form trigeminal and sacral ganglia of the infected mice was observed in vitro. Results Weight loss and histopathological lesions were observed in the mice of the experimental group 6 d after infection. Major pathological changes in the HSV-2-infected mice through nasal tract inoculation involved the lung and central nervous system (CNS), including alveolar wall congestion, cerebrovascular cuff response and lymphocyte infiltration. However, the major lesions in the infected mice through genital tract inoculation were found in the reproductive ducts, such as sacral ganglion necrosis, eosinophilia in the vagina and uterus, and ovarian congestion. Results of the viral load detection in tissues and organs of the infected mice were consistent with the pathological changes. The mice infected through nasal tract inoculation had significantly higher viral loads in the nerves and lungs than those by genital tract inoculation, but lower viral loads in the genital tracts and sacral ganglia. Positive expression of lat gene at mRNA level was detected in the trigeminal and sacral ganglia of mice with HSV-2 latency 28 d after infection. In addition, both of the tissue fragments from trigeminal and sacral ganglia had cytopathic effec

关 键 词：单纯疱疹病毒Ⅱ型 生殖道感染 鼻腔感染 病理学分析 

分 类 号：R752.11[医药卫生—皮肤病学与性病学]