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

Abstract

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 effects (CPEs) on Vero cells. Enhanced expression of lat gene at mRNA level and much severer CPEs were induced by genital tract inoculation than by nasal tract inoculation. Conclusions HSV-2 could infect and cause histopathological damages in BALB/c mice through both nasal and genital tracts. In addition, the locations of the pathological lesions were closely related to the mode of infection. Key words: Herpes simplex virus type Ⅱ (HSV-2); Genital tract infection; Nasal tract infection; Pathological analysis