| Herpes simplex virus type 2(HSV-2)commonly causes infections globally,and the prevalence was estimated to be 16%in the general population 15 to 49 years.HSV-2 can be spreads widely high morbidity not only because HSV-2 has a special replication and a strong tropism to host epithelial tissues,but also because human sexual activity and reproduction provide frequent contact with the pathogen.To prevent and treat infection of HSV-2,antiviral drugs such as acyclovir can alleviate the symptoms of herpes diseases in human,it does not completely eliminate the latent infectionly.Therefore,HSV-2 vaccine is imminent.To systematically understand the pathological mechanism of HSV-2 infection,we need to the interaction between the virus and the various components in host cells and tissues during the infection process.Meanwhile,elucidating the pathological mechanism of HSV-2 is also important for the development of HSV-2 vaccine.In this study,adult BALB/c mice were infected by wild-type HSV-2 HG52 strain through respiratory and genital tract.The clinical characteristics and pathological changes of infected mice were compared and analyzed.Then,we demonstrated the nervous tissue tropism of HSV-2 latent infection and carried out a reactivation test of latent infection of the relevant neural tissue in vitro.We primarily compared the clinical symptoms of different infection route of mice under low-dose treatment.The weight of mice infected by HSV-2 through both respiratory and genital routes were all decreased after six-day post infection whenich compared with the control group.In the 56-day observation period,mouse infected with HSV-2 did not die.Further pathological analysis showed that the same dose of HSV-2 infection through the respiratory tract and genital tract can cause corresponding pathological damage in various tissues of mouse.Mice infected by HSV-2 through respiratory mainly showed the pathological injury of alveolar wall hyperemia,cerebrovascular cuff,trigeminal nucleus with deeply stained and solidified,and lymphocyte infiltration in spinal cord.The main pathological features of the mice infected through respiratory tract were sacral ganglion nerve fiber disorder,a small amount of calcification and necrosis,increased basophilic granulocyte basophil in the vagina and uterus in the reproductive system tissues,and partial hyperemia in the ovaries.In addition,the distribution of viral load of the two infection routes in the corresponding tissues and organs was consistent with the pathological results.HSV-2 was mainly detected in brain,spinal cord,tergeminal and lung tisuses of mice infected through the respiratory tract,while abundant virus was detected in vaginal,uterus,ovary and sacral ganglia of mice infected through genital route.The results of virus detection experiments in mouse neural tissue at after 28 days after primary infection showed that the positive signals of the HSV-2 LAT mRNA were observed in the trigeminal and sacral ganglia of both route infected mice.It indicated that HSV-2 can form latent infections in the nervous tissues through different infection routes.In addition,reactivation test in vitro showed that the latent viruses in isolated mouse trigeminal and sacral ganglion tissues can be reactivated on cultured Vero cells.And a higher level of HSV-2 reactivation was observed in the mice group infected through genital tract when compared with the mice infected by respiratory infection route.In conclusion,the overall results of this study revealed that by using BALB/c mice model infected with HSV-2,both respiratory and genital infection routes can cause corresponding pathological damage and present viral infections in various tissues.This animal model provides a tool or further examination of interaction of HSV-2 and the host immune system under the different infection routes.The current results it may also provide somes clues for the application of therapeutic drugs and the development of HSV-2 vaccines. |
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