Ⅰ型单纯疱疹病毒致小鼠面神经麻痹的实验性研究

【摘要】目的建立Ⅰ型疱疹病毒感染致小鼠面神经麻痹的动物模型，并探讨单纯疱疹病毒1型（herpes simplex virus type1，HSV-1）在小鼠面神经麻痹发生过程中的致病机制及作用部位。方法选择53只16-18g、4周龄雌性Balb／e小鼠，用26G针头在49只实验组小鼠右耳廓背面近耳根部皮肤连续搔刮后，将25μL HSV-1病毒液滴在创面上。同样方法搔刮左耳廓，滴25μL PBS作为对照。另4只动物不作处理，作为空白对照。PCR法检测接种病毒后不同时问段的实验动物相关部位的HSV-1DNA表达。结果49只接种动物中，37只（75、5l％）出现不同程度的面神经麻痹。其中，右侧14只（14／37，37．84％），左侧3只（8、11％），双侧20只（54．05％）。20只双侧面神经麻痹动物中，13只（65％）先出现右侧面神经麻痹，2只（10％）先出现左侧面神经麻痹，另外5只直接发生双侧面神经麻痹。37只面神经麻痹动物中，6只（16．22％）面神经麻痹自行恢复，平均恢复时间为7．83d。结论HSV-1存在于脑干和大脑皮层面神经运动核放射区与面神经麻痹的出现关系密切。     

Cochlear changes after herpes simplex virus infection

After direct inoculation of herpes simplex virus (HSV) into the scala tympani of the guinea pig, the tectorial membrane showed various morphological changes: atrophy, roll-up and dot formation. Immunofluorescent and electronmicroscopic studies revealed that the changes were due to HSV infection. The findings were compared with those observed in the temporal bones of a 77-year-old patient who suffered from sudden deafness. The tectorial membranes of both temporal bones showed various changes identical with those observed in experimental viral labyrinthitis. This supports the view that sudden deafness in this particular patient was of viral origin. In the animal experiment, HSV antigen could be detected from the cochlea of the non-inoculated side, which was morphologically normal. Further study is required to reactivate HSV in the cochlea with latent infection. This animal can probably be used as an animal model for sudden deafness.     

Effects of acyclovir on facial nerve paralysis induced by herpes simplex virus type 1 in mice

OBJECTIVES: Bell's palsy has recently been claimed to be caused by herpes simplex virus type 1 (HSV-1) infection. The anti-viral agent acyclovir is a specific inhibitor of herpesvirus replication, and the most effective agent for the treatment herpesvirus infection. The purpose of this experiment was to assess the effect of acyclovir on the facial nerve paralysis included by HSV-1 infection. METHODS: We succeeded in producing an animal model of acute and transient facial nerve paralysis induced with HSV-1 neuritis simulating human Bell's palsy. In this study, acyclovir administration was performed before and after facial nerve paralysis, and continued for 5 days. Controls were given phosphate-buffer saline (PBS) instead of acyclovir, and the incidence and duration of facial nerve paralysis was compared in the acyclovir groups and controls. RESULTS: The incidence of facial nerve paralysis was significantly lower in the group given acyclovir before the paralysis than in the controls, and the duration of facial nerve paralysis was shorter. CONCLUSIONS: Administration of acyclovir before the paralysis reduced the incidence and duration of facial nerve paralysis. Administration of acyclovir after the paralysis improved the duration of facial nerve paralysis.     

小鼠病毒性面神经炎模型中面神经元凋亡的研究

目的 探讨1型单纯疱疹病毒（herpes simplex virus type 1,HSV-1）性面神经炎动物模型中面神经运动神经元（facial motor neurons,FMN）的凋亡情况以及凋亡相关基因bcl-2和bax的表达。方法 Balb/c小鼠84只,分别进行HSV-1接种和面神经切断处理。在操作后第1、3、7、10、15、20及30天分批处死动物,对面神经核进行HE染色、尼氏染色;采用原位末端转移酶标记（terminaldeoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling,TUNEL）技术检测FMN的凋亡;免疫组化染色检测凋亡相关基因bcl-2和bax在FMN中的表达。结果 面神经切断后,同侧FMN出现凋亡,在第10、15天达高峰,Bcl-2表达降低,Bax表达升高,Bcl-2/Bax比值下降;接种病毒后,同侧FMN没有明显的细胞凋亡,Bcl-2表达增高,在第15天达高峰,Bcl-2/Bax比值上升。结论 小鼠面神经接种HSV-1后FMN没有明显凋亡,可能与神经损伤程度轻以及HSV-1抑制宿主细胞凋亡有关,Bcl-2、Bax可能参与调控FMN的凋亡。     

Bell's palsy and herpes simplex virus

The possible association of some viral infections with the onset of Bell's palsy was examined in a study of 142 patients. The number of probable recent viral infections, as judged by increase in antibody titers or presence of IgM antibodies, did not differ statistically from that found in a sex- and age-matched control group. However, a higher prevalence of herpes simplex virus (HSV) antibodies was found in the patient group with both a complement-fixation (CF) test and a radioimmunoassay (RIA). Moreover, titers of HSV CF antibodies and antibodies against HSV envelope antigens (RIA) were higher in the patient group. The possibility of reactivated HSV infection and transient demyelination of the facial nerve being causatively associated with Bell's palsy is discussed.     

Oral manifestations of herpes simplex virus infections

Most individuals are infected with Herpes Simplex in childhood usually suffering a mild febrile illness of no consequence. Later some individuals suffer recurrent infections which appear as cold sores on the lip while others intermittently shed virus in the oro-pharygeal secretions. Adults uninfected in childhood may be exposed to viruses for example by kissing and develop an acute primary herpes with fever and gingivo-stomatitis occasionally requiring hospital admission. Awareness of this condition is required for diagnosis after which the majority of patients seen in otolaryngological practice need only supportive therapy, explanation and reassurance. Recurrent cold sores are no more than a nuisance in most patients, but occasionally they are severe and in others the cold sore may precipitate oral erythema multiforme. Unfortunately the treatments available for recurrent cold sores are rather unsatisfactory.     

Reactivation of herpes simplex virus type 1 and varicella-zoster virus and therapeutic effects of combination therapy with prednisolone and valacyclovir in patients with Bell's palsy

OBJECTIVES: To determine whether reactivation of herpes simplex virus (HSV) type 1 or varicella-zoster virus (VZV) is the main cause of Bell's palsy and whether antiviral drugs bring about recovery from Bell's palsy. STUDY DESIGN: Randomized, multicenter, controlled study. METHODS: One hundred fifty patients with Bell's palsy were enrolled in this study. The patients were randomly assigned to a prednisolone group or a prednisolone-valacyclovir group, in whom virologic examinations for HSV-1 and VZV were performed by simple randomization scheme in sealed envelopes. The recovery rates among various groups were analyzed using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Reactivation of HSV-1, VZV, and both viruses was detected in 15.3%, 14.7%, and 4.0% of patients, respectively. There was no significant difference in recovery rates between the prednisolone group and the prednisolone-valacyclovir group, although recovery in the patients with HSV-1 reactivation tended to be higher in the prednisolone-valacyclovir group than in the prednisolone group. There was a significant difference in recovery among age groups and between individuals with complete and incomplete paralysis. CONCLUSIONS: Reactivation of HSV-1 or VZV was observed in 34% of the patients with Bell's palsy. The effect of combination therapy with prednisolone and valacyclovir on recovery was not significantly higher than that with prednisolone alone.     

Ménière's disease and antibody reactivity to herpes simplex virus type 1 polypeptides.

PURPOSE: It has been reported that the inner ear is capable of responding to antigen challenge. In this study, we have investigated the antibody reactivity to herpes simplex virus 1 (HSV-1) proteins in sera from patients with Ménière's disease. PATIENTS AND MATERIALS: Serum from 21 patients scheduled to undergo endolymphatic sac decompression for Ménière's disease was obtained. The sera from 21 age- and sex-matched individuals without a history of ear disease served as the control. An enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies to HSV-1, HSV-2 cytomegalovirus (CMV), varicella-zoster virus (VZV), and measles virus. Immunoblotting was used to confirm and further evaluate the HSV-1 antibody response. RESULTS: All but one patient had antibodies to HSV-1. ELISA mean log titers were significantly lower in the patient group to CMV and VZV when compared with controls. A pattern of generally higher antibody reactivity in patients with Ménière's disease was demonstrated to the individual SDS-PAGE HSV-1 polypeptides as judged by immunoblotting. CONCLUSION: The HSV-1 antibody response found in patients with Ménière's disease may indicate viral reactivation and denotes the importance of further studies on the role of infectious agents in this disease.     

Role of T-lymphocyte subsets in facial nerve paralysis owing to the reactivation of herpes simplex virus type 1

CONCLUSION: Although both T-cell subsets are essential for inhibiting HSV-1 reactivation in the GG, CD4 + T cells play a more important role in host defense against virus replication. OBJECTIVE: To elucidate the host immunological factors that participate in herpes simplex virus type 1 (HSV-1) reactivation in the geniculate ganglia (GG) and lead to facial paralysis, we developed a mouse model of facial paralysis that involved the reactivation of HSV-1 following general immune suppression. MATERIAL AND METHODS: Eight weeks after recovery from primary facial paralysis caused by inoculating the auricle with HSV-1 the auricle was scratched and mice (n = 69) were given an i.p. injection of either anti-CD4 (n = 46) or anti-CD8 (n = 23) monoclonal antibody to deplete specific T-lymphocyte subsets. Following this reactivation procedure, the rate of recurrent facial paralysis was compared between the two models. The GG were examined histopathologically and using polymerase chain reaction to detect HSV-1 DNA. RESULTS: Facial paralysis developed in 42% of mice in the anti-CD4 model and in 13% in the anti-CD8 model. HSV-1 DNA was detected in 50% of the mice in both models. Histopathologically, neurons were destroyed in parts of the GG and numerous virus particles were seen in the surviving neurons.     

Role of T-lymphocyte subsets in facial nerve paralysis owing to the reactivation of herpes simplex virus type 1

Conclusion. Although both T-cell subsets are essential for inhibiting HSV-1 reactivation in the GG, CD4+ T cells play a more important role in host defense against virus replication. Objective. To elucidate the host immunological factors that participate in herpes simplex virus type 1 (HSV-1) reactivation in the geniculate ganglia (GG) and lead to facial paralysis, we developed a mouse model of facial paralysis that involved the reactivation of HSV-1 following general immune suppression. Material and methods. Eight weeks after recovery from primary facial paralysis caused by inoculating the auricle with HSV-1 the auricle was scratched and mice (n=69) were given an i.p. injection of either anti-CD4 (n=46) or anti-CD8 (n=23) monoclonal antibody to deplete specific T-lymphocyte subsets. Following this reactivation procedure, the rate of recurrent facial paralysis was compared between the two models. The GG were examined histopathologically and using polymerase chain reaction to detect HSV-1 DNA. Results. Facial paralysis developed in 42% of mice in the anti-CD4 model and in 13% in the anti-CD8 model. HSV-1 DNA was detected in 50% of the mice in both models. Histopathologically, neurons were destroyed in parts of the GG and numerous virus particles were seen in the surviving neurons.     

Adult supraglottitis due to herpes simplex virus

Changes in the concepts regarding epiglottis have occurred over the last two decades. Supraglottis, once thought to occur exclusively in the pediatric population, is now recognized in adults. Supraglottis is a well-defined syndrome usually caused by a bacterial infection by Haemophilus influenzae type B. Recently, other organisms have been implicated as etiologic agents in cases of supraglottitis. Documented viral supraglottitis is very rare, and adult supraglottitis due to herpes simplex virus-I has not been reported to our knowledge.     

Neonatal stridor in association with herpes simplex infection of the larynx

Herpes simplex virus (HSV) infection in the neonatal period may be confined to the eyes, skin and upper aerodigestive tract or may be widely disseminated to other organs, with particular recognition of involvement of the central nervous system (CNS) causing herpes encephalitis (Whitley et al., 1980a, b; Andersen, 1987). Primary laryngeal HSV infection is extremely uncommon. We present a case of acute neonatal stridor secondary to such localized disease and discuss its management.     

Atypical oral presentation of herpes simplex virus infection in a patient after orthotopic liver transplantation

An atypical oral presentation of herpes simplex virus infection in a 49-year-old woman after orthotopic liver transplantation is reported. Clinically, the differential diagnosis included chronic hyperplastic candidiasis, nodular leukoplakia of undetermined etiology, and malignant neoplasm. An excisional biopsy revealed herpesvirus infection, and immunoperoxidase staining confirmed herpes simplex virus infection. This report describes the clinical and histologic appearance of these lesions and the course and treatment of the patient.     

New strategies against drug resistance to herpes simplex virus

Herpes simplex virus (HSV), a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir (ACV) and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets (the DNA helicase/primase (H/P) complex), new types of molecules (nature products) and new antiviral mechanisms (lethal mutagenesis of Janus-type nucleosides) to fight the drug resistance of HSV.     

单纯疱疹病毒性面神经炎的动物模型

目的建立单纯疱疹病毒1型（herpes simplex virustype 1，HSV-1）感染造成的面神经麻痹动物模型，研究HSV-1与面神经麻痹之间的关系。方法Balb／c小鼠66只，切断双侧面神经耳后支，右侧神经断端接种HSV-1，左侧接种胎牛血清作为对照。观察小鼠全身情况、双侧面肌运动的对称性；颞骨连续切片HE染色；颞外段面神经锇酸染色；双侧面神经、脑干、三叉神经节、脊髓行PCR检测HSV-1 DNA片断。结果28只小鼠（42．42％）于接种后2～5d发生右侧面神经麻痹，病程持续3～6d后恢复。38只未发生面神经麻痹。与对侧比较，颞骨连续切片显示面神经麻痹鼠右侧神经肿胀、神经周围问隙变小、炎细胞浸润，面神经横截面秽面神经管横截面积的比值明显变大；颞外段面神经出现神经髓鞘变薄、脱失。面神经麻痹鼠和无面神经麻痹鼠的部分神经组织中检测到HSV DNA。结论在面神经耳后支断端接种HSV-1可以引起小鼠暂时性面神经麻痹，可能是由于病毒逆行转运引起面神经炎，进而神经肿胀受压发生面神经麻痹。     

Detection of herpes simplex virus, varicella zoster virus and cytomegalovirus in aphthous stomatitis

Attempts were made to demonstrate herpes simplex virus (HSV) type 1 and type 2, varicella zoster virus (VZV) and cytomegalovirus (CMV) in specimens obtained from aphthous ulceration lesions by the immunofluorescent method using fluorescein-labeled monoclonal antibodies. HSV-1 and VZV were detected in 2 and 4 out of 30 patients, respectively. Although almost all viruses that can infect the oral cavity could occasionally cause stomatitis, neither HSV-2 nor CMV was not found in this study. VZV was detected in 1 out of 8 patients with recurrent aphthous ulceration. After treatment with acyclovir, the patient's symptoms has become less severe and recurrence rates of attacks reduced, however, the patient has not been totally free of the disease. There were no differences in clinical aspects of stomatitis between the patients with and without viral isolation. Further clinical investigation is encouraged to confirm the relationship between aphthous stomatitis and viral infection.