Differences In Clinical,Pathological And Etiological Features Of Herpes Simplex Virus 1 Infection In Different BALB/c Mouse Models

Herpes Simplex Virus type 1(HSV1)with a more than 50%infection rate in human population can cause oral herpes,herpetic keratitis,herpetic encephalitis and genital herpes disease in different age groups.It can form latent infection in ganglion(especially the trigeminal ganglia),and be reactivated to a new round hyperplastic infection after stimulation,causeing pathological damage to affect the patient's quality of life.At present,there are still unclearly for the study of HSV1 infection.Therefore,establishing a proper HSV1 infection animal model and evaluating system including clinical symptom,pathology phenomenon and pathogen proliferation characteristics,could be of great significance to study the pathological mechanism of HSV1 infection.Currently,the main animal model for herpes virus infection are guinea pigs,rats,mice,rabbits and so on.The mice with its advantage of clear background,simply operated and cheap,are widely used in experimental study.Preliminary data show that BALB/c mice is frequently used as an animal model which has the high infection rate during acute infection of HSV1 and do not easily relapse after viral latent infection.In many studies about mice infected HSV1,strains,infection routes and the species of mice are often different.Therefore,the corresponding contrast analysis is often difficult to unified conclusion.This study based on early data investigated the related clinical manifestations,pathological features and characteristics of viral distribution in tissues and organs in BALB/c mice infected different HSV1 strains through different methods.We also learned comprehensively infection status of different strains under different conditions and completed the comprehensive comparative study for different strains infections under different conditions getting the corresponding systematic data.These results are not only of great significance to understand the clinical,pathological,etiological process after HSV1 infection,but also can provide meaningful relevant data for reference index system which applied to evaluate the HSV1 experimental vaccine.Generally,different strains and different innoculation route may cause differences on immune responding of the mice in the infection.Meanwhile,varieties of mice have different MHC genetic background which make its susceptibility to virus may be different.On the premise of comprehensive consideration for above factors,we established an acute infection model with different week-old BALB/c mice challenged by HSV1 17+ and McKrae strains via intranasal and corneal ways.Additionally,we also constructed a chronic infection model with BALB/c mice by subcutaneous and foot pad inoculation.And this study comparatively analyzed the changes on clinical symptom,pathology phenomenon,etiology distribution in animals infected by the HSVI,and providing the relevant different data for the further research about HSVI infection mice in laboratory.Although all experimental mice showed trichiasis and roachback after infection,there were differences in weight and fatality rate among different groups.Results of the quantitative PCR detection indicated that the proliferation of HSVI in the nervous tissues(brain,spinal cord,trigeminal,ganglion)varied among different groups.The pathological examination indicated that in the acute infection groups,significant pathological changes only occurred in the brain tissues,while in the chronic infection groups,pathological injuries only occurred in the trigeminal ganglia.Although a key index latency-associated transcript(LAT)was not detected in the trigeminal nerve tissues of mice in the chronic infection groups,coculturing the tissues with Vero cells resulted in infectious lesions in the cells.This study indicates that there are significant differences in weight and fatality rate among different BALB/c mouse models of HSV1 infection.Varied replication dynamics of HSV1 were observed in tissues or organs of the BALB/c mice in different groups.Therefore,different indexes should be adopted to evaluate different HSV1 infection models.