Low numbers and altered phenotype of invariant natural killer T cells in recurrent varicella zoster virus infection

Invariant natural killer T (iNKT) cells play an important role in the immune response against various infectious agents. In this study we investigated their role in human defense against the varicella zoster virus. We observed decreased numbers of iNKT cells in patients who failed to control latent varicella zoster virus infection, e.g. underwent several reactivations of the virus. The residual population of iNKT cells expressed significantly higher levels of inhibitory receptor CD158a that was further up-regulated in the course of acute viral infection. Both of these abnormalities might contribute to impaired control of varicella zoster virus in human.     

带状疱疹后遗神经痛的动物模型及病理机制研究

带状疱疹后遗神经痛(postherpetic neuralgia,PHN)是带状疱疹最常见的并发症,其发生率随年龄的增加而增加,并且严重影响患者的生活质量。目前PHN的治疗多采用复合用药,但效果不佳。阻碍其治疗发展的关键是对PHN的发病机制不甚清楚,究其根本原因是缺乏与临床符合的动物模型。目的:综述带状疱疹病毒感染模型的改良和进展,使PHN的病理机制得到进一步揭示。内容:介绍与PHN相关的水痘-带状疱疹病毒潜伏感染模型、体外模型及慢性感染模型,综述与PHN发生发展有关的潜伏机制、与其他神经病理性痛相似的机制及近年来较为关注的中枢与外周损伤机制。趋向:进一步研究与人类水痘带状疱疹病毒感染更为相似的动物模型,并随其改良和进展,使发生PHN的机制得到进一步的阐释。     

多瑞吉在带状疱疹疼痛治疗阿片类药物转换中的应用

目的:探讨多瑞吉在带状疱疹疼痛治疗阿片类药物转换中的应用。方法:选择37例住院治疗的带状疱疹疼痛患者,年龄>45岁、VAS评分≥4分、所有病人常规抗病毒治疗、增加免疫力等常规治疗,予硬膜外腔置管间断注入消炎镇痛药物并持续泵吗啡,根据疼痛调整至止痛剂量,转换为多瑞吉贴剂后出院。疼痛控制后逐渐减药,每半个月减量半贴多瑞吉,对病人的疼痛评分、生活质量及并发症进行评估。结果:有1例病人应药物副反应出组,其余病人硬膜外泵吗啡后均在一周左右控制疼痛,等效转换为多瑞吉,定时定量减药,无疼痛反复,成瘾戒断等情况。结论:带状疱疹疼痛采用硬膜外间断注药持续泵吗啡迅速达到无痛后,转换为等效剂量的多瑞吉,定时定量减药,安全有效。     

2′-Fluorosugar analogues of the highly potent anti-varicella-zoster virus bicyclic nucleoside analogue (BCNA) Cf 1743

We report the preparation of 2′-α-F, 2′-β-F and 2′,2′-difluoro analogues of the leading anti-varicella zoster virus (VZV) pentylphenyl BCNA Cf 1743. VZV thymidine kinase showed the highest phosphorylating capacity for the β-fluoro derivative, that retained equal antiviral potency as the parent compound. In contrast, the α-fluoro- and 2′,2′-difluoro BCNA derivatives were markedly less (100-fold) antivirally active.     

Varicella zoster virus vaccines: potential complications and possible improvements

Varicella zoster virus(VZV) is the causative agent of varicella(chicken pox) and herpes zoster(shingles). After primary infection, the virus remains latent in sensory ganglia, and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine(v-Oka) is highly attenuated in the skin, yet retains its neurovirulence and may reactivate and damage sensory neurons. The reactivation is sometimes associated with postherpetic neuralgia(PHN), a severe pain along the affected sensory nerves that can linger for years, even after the herpetic rash resolves. In addition to the older population that develops a secondary infection resulting in herpes zoster, childhood breakthrough herpes zoster affects a small population of vaccinated children. There is a great need for a neuro-attenuated vaccine that would prevent not only the varicella manifestation, but, more importantly, any establishment of latency, and therefore herpes zoster. The development of a genetically-defined live-attenuated VZV vaccine that prevents neuronal and latent infection, in addition to primary varicella, is imperative for eventual eradication of VZV, and, if fully understood, has vast implications for many related herpesviruses and other viruses with similar pathogenic mechanisms.     

The varicella-zoster virus-mediated delayed host shutoff: open reading frame 17 has no major function, whereas immediate-early 63 protein represses heterologous gene expression

We reported that varicella-zoster virus (VZV) causes a delayed host shutoff during its replicative cycle. VZV open reading frame 17 (ORF17) is the homologue of the herpes simplex virus (HSV) UL41 gene encoding the virion host shutoff (vhs) protein which is responsible for the shutoff effect observed in HSV-infected cells. In the present study, we demonstrated that ORF17 is expressed as a late protein during the VZV replicative cycle in different infected permissive cell lines which showed a delayed shutoff of cellular RNA. A cell line with stable expression of VZV ORF17 was infected with VZV. In these cells, VZV replication and delayed host shutoff remained unchanged when compared to normal infected cells. ORF17 was not capable of repressing the expression of the beta-gal reporter gene under the control of the human cytomegalovirus immediate-early gene promoter or to inhibit the expression of a CAT reporter gene under the control of the human GAPDH promoter, indicating that ORF17 has no major function in the VZV-mediated delayed host shutoff. To determine whether other viral factors are involved in the host shutoff, a series of cotransfection assays was performed. We found that the immediate-early 63 protein (IE63) was able to downregulate the expression of reporter genes under the control of the two heterologous promoters, indicating that this viral factor can be involved in the VZV-mediated delayed host shutoff. Other factors can be also implicated to modulate the repressing action of IE63 to achieve a precise balance between the viral and cellular gene expression.     

He—Ne激光治疗带状疱疹神经痛

４３例带状疱疹病人随机分为Ｈｅ－Ｎｅ激光治疗组（２９例）及红外线对照组（１４例）,分别进行局部治疗（两组全身用药相同）。采用“６点行为疼痛测定法”对治疗期及治疗完成时的神经痛程度客观评分,经方差分析,治疗期及治疗后的结果显示激光治疗组的疗效明显优于对照组（ｐ＜０．０５～０．０１）;３月后随访,疱疹后神经痛的发生率两组相比亦有显著性差异（ｐ＜０．０１）。并对Ｈｅ－Ｎｅ激光在治疗带状疱疹神经痛的作用机理进行了讨论。     

随机扩增多态性技术联合荧光定量高敏检测三种疱疹病毒方法的建立

目的:建立一种随机扩增多态性技术(RAPD)联合荧光定量聚合酶链式反应(q PCR)高敏定量检测单纯疱疹病毒(HSV)、人类巨细胞病毒(HCMV)、水痘带状疱疹病毒(VZV)的新方法。方法:根据文献筛选出数十条随机引物,分别对三种疱疹病毒进行随机扩增,产物经2%琼脂糖凝胶电泳,选取稳定清晰条带进行分离、纯化及克隆测序,应用blast-nr比对genebank现有病毒序列,选取高于99%匹配度的基因序列作为目的片段,并在其内部用primer3.0设计特异性内引物。经过引物筛选及条件优化后建立RAPD联合q PCR检测新方法,分别检测三种疱疹病毒。结果:经过筛选,确定了HSV、HCMV、VZV扩增灵敏性及特异性最好一组引物,建立的RAPD-q PCR可分别检测出1:10~6 HSV、1:10~5 HCMV和1:10~5 VZVDNA,而单一q PCR仅能检测1:10~3 HSV、1:10~2HCMV和1:103 VZVDNA。RAPD-q PCR相比于单一q PCR灵敏性提高100-1000倍,RAPD-q PCR扩增大于1:10~5病毒DNA得到的CT值均小于22.96±0.81,与10~2 copies/μL的标准线相距远,易于区分阴性和阳性。此外,用乙型肝炎病毒及疱疹病毒互为对照未见非特异扩增,特异性好。结论:随机扩增多态性技术联合荧光定量是一种检测三种病毒高度灵敏及特异的检测方法。     

水痘—带状疱疹病毒地方分离株在兔脑神经细胞中的形态与形态发生特征

为阐明水痘－带状疱疹病毒济南分离株（VZVJ1）在兔脑神经细胞（RNC）中的形态与形态发生特征,我们利用超薄切片电子显微镜技术对感染VZVJ1的RNC进行了观察研究。结果表明：RNC在感染VZVJ1 6h后核内右见散在的核衣壳,12h后细胞核和细胞质内核衣壳明显增多,24h达高峰,而细胞核和细胞质内的成熟病毒颗粒较少见,病毒大小、形态基本一致,呈圆形或椭圆形,核心直径30－50nm,核衣壳74－96nm,成熟病毒110－180nm。核衣壳内有3种类型的核心,即电子致密核心、部分致密核心和电子透明核心,细胞核和细胞质内均可见核心样电子致密体和布纹样结构,在细胞质仙还可见少量“繁残复合体”,由膜性结构包绕多个囊泡构成,提示VZVJ1在RNC中的形态发生不同于其它性质的细胞。     

剪夏罗鲜汁及黄酮组分对体外Ⅰ型单纯疱疹病毒的抑制作用

在人胚肺纤维母细胞体外培养系统中,以微量单层细胞病变法观察剪夏罗（ＬｙｃｈｎｉｓｃｏｒｏｎａｔａＴｈｕｎｂ．）鲜汁液及其黄酮组分对体外Ⅰ型单纯疱疹病毒增殖性感染的抑制作用。剪夏罗高浓度鲜汁液（１∶５０、１∶２０及１∶１０稀释液）及其高浓度黄酮组分Ⅰ、Ⅱ（＞１００μｇ／ｍｌ）对细胞有明显的毒性作用;剪夏罗鲜汁液１∶１００～１∶４００稀释液,可明显抑制病毒复制,使病毒诱导的细胞病变明显减轻,培养液中子代病毒感染滴度明显下降,且培养上清液中病毒感染滴度与鲜汁液和黄酮组分的浓度呈直线负相关;剪夏罗鲜汁液的黄酮组分Ⅰ、Ⅱ在１０μｇ／ｍｌ～０１μｇ／ｍｌ浓度范围内对病毒诱导的细胞病变有明显的抑制作用。