Human herpesvirus 7 meningitis in an adolescent with normal immune function:A case report

BACKGROUND Human herpesvirus type 7(HHV-7)is a less common herpes virus that usually causes mild,self-limiting illnesses.However,in recent years,there have been increasing reports of HHV-7 causing serious central nervous system infections,especially meningitis.The pathogenesis and clinical features of HHV-7 meningitis,particularly in adolescents with normal immune function,remain incompletely studied.Therefore,the purpose of this report is to share a case of HHV-7 meningitis in an immunocompetent adolescent with a view to deepening our understanding of the disease.CASE SUMMARY A 12-year-old female was admitted with fever,headache,and vomiting.4 d before admission,the patient developed a fever without obvious induction,with a temperature up to 39.5℃,no convulsions,accompanied by chills,headaches,fatigue,and no muscle aches.The patient was treated with fever reduction,which could be reduced to 38℃;repeated high fever,accompanied by vomiting 7-8 times;and no abdominal pain or diarrhea.The patient was diagnosed with"acute suppurative tonsillitis"in a local hospital,and the blood routine was generally normal.The patient was given symptomatic support treatment such as"ceftriaxone sodium"and antiemetic rehydration for 2 d,and his condition did not improve.The patient's physical examination showed pharyngeal congestion,bilateral tonsil grade I hypertrophy,regression of purulent secretions,and cervical resistance.Ocular B-ultrasound:Opacity of the vitreous body and edema of the optic disc in both eyes.Optical coherence tomography examination showed that the macular fovea was generally normal in both eyes,with edema of the optic disc.DNA virus monitoring results:HHV-7.We gave ganciclovir antiviral therapy,dexamethasone anti-inflammatory treatment,mannitol to reduce cranial pressure,omeprazole to protect gastrointestinal mucosa,and calcium and potassium supplementation.CONCLUSION This study reports a case of HHV-7 meningitis in an adolescent with normal immune function.Through comprehensive analysis of the clinical manifestations,laboratory tests,and treatment methods of the patient,it is found that early identification and antiviral treatment are essential for the outcome of the disease.This case suggests that despite normal immune function,adolescents may still suffer from herpes virus type 7 meningitis,so clinicians should be vigilant and take effective treatment measures in time.

Genotypic analysis on the ORF-K1 gene of human herpesvirus 8 from patients with Kaposi's sarcoma in Xinjiang,China

Human herpesvirus 8 （HHV-8） is thought to be essential for the development of all forms of Kaposi＇s sarcoma （KS）. HHV-8 DNA is present virtually in all KS tumor biopsy samples. Genes at both ends of the HHV-8 genome have been shown to vary considerably. Seven major molecular subtypes of HHV-8 were defined based on the amino acid sequence of the open reading frame K1 （ORF-K1）, generally known as A, B, C, D, E, F, and Z. Most strains collected worldwide were clustered into two subtypes （A and C）. Here, the K1/VRI region of HHV-8 was amplified by nested PCR in 22 （81.48%） of 27 cases from Xinjiang Uygur Autonomous Region, a province in northwestern China. Phylogenetic analysis on the basis of the K1/VR1 amino acid sequence indicated that the majority of these KS patients were infected by subtype C HHV-8 （n = 18, including 15 belonging to the C2 group）, and several by subtype A （n = 4, including 3 being the A1 group）. This is the first report of subtype A HHV-8 in China. Furthermore, the correlations between different forms and lesions of KS and different subtypes of HHV-8 were analyzed. The findings showed that subtype A HHV-8 resulted in significantly more frequent mucosal KS lesions than subtype C. However, there was no obvious correlation between different forms of KS and different subtypes of HHV-8.

Contributions of neurotropic human herpesviruses herpes simplex virus 1 and human herpesvirus 6 to neurodegenerative disease pathology

Human herpesviruses （HVs） have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system （CNS）. The ability of HVs to enter a state of latency, a defining char- acteristic of this viral family, allows them to persist in the human host indefinitely. As such, HVs represent the most frequently detected pathogens in the brain. Under constant immune pressure, these infections are largely asymptomatic in healthy hosts. However, many neurotropic HVs have been directly connected with CNS pathology in the context of other stressors and genetic risk factors. In this review, we discuss the potential mechanisms by which neurotropic HVs contribute to neurodegenerative disease （NDD） patholo- gy by highlighting two prominent members of the HV family, herpes simplex virus 1 （HSV-1） and human herpesvirus 6 （HHV-6）. We （i） introduce the infectious pathways and replicative cycles of HSV-1 and HHV-6 and then （ii） review the clinical evidence supporting associations between these viruses and the NDDs Alzheimer＇s disease （AD） and multiple sclerosis （MS）, respectively. We then （iii） highlight and dis- cuss potential mechanisms by which these viruses exert negative effects on neurons and glia. Finally, we （iv） discuss how these viruses could interact with other disease-modifying factors to contribute to the initiation and/or progression of NDDs.

Reactivation of Latent Infection of Human Herpesvirus 8 in BC-3 Cells from Primary Effusion Lymphoma by Recombinant CytokinesSimilar to that Produced by HIV-1-infected T Cells

Objective: To study and confirm that recombinant cytokines similar to those produced by HIV-1 infected T cells induced lytic cycle replication of human herpesvirus 8 (HHV-8) in BC-3 cells, another cell line from primary effusion lymphama(PEL). Methods: The persistent stimulation of BC-3 was conducted by several cytokines known to be produced by HIV-1-infected T cells and important in growth and proliferation of Kaposi's sarcoma(KS)cells in vitro, such as the interferon-γ (IFN-γ) , tlie hepatocyte growth factor/scatter factor (HGF / SF) , the Oncostain M(OSM) , and the tumor necrosis factor-α (TNF-α)which is not produced by HIV-1-infected T cells. Treated and untreated BC-3 cells were collected at the 3rd and 7th day of persistent stimulation, respectively. Immuno-histochemical (IHC) staining, Northern blot, quantitative PCR (real- time PCR ) and electron microscopy (EM) were carried out to detect the expression of immunogenic protein ORF59, messenger RNA (mRNA) of minor capsid protein ORF26, and the presence of viral particles of HHV-8 from treated and untreated BC-3 cells. Results: It showed that IFN-γ, HGF/SF, OSM, and TNF-α were found to induce an increase in mRNA expression of ORF26 when added individually to BC-3 cells. Particularly, ORF26 expression stimulated with IFN-γ and TNF-α respectively, increased 6. 1 and 2. 5-fold(from real-time PCR results)at the 7th day when compared with untreated BC-3 cells. Meanwhile, about 20% of IFN-γ stimulated BC-3 cells expressed ORF59 at the 7th day as compared with 1. 5% of untreated BC-3 cells when IHC staining was employed. In addition, viral particles of HHV-8 were readily identified in BC-3 cells stimulated with IFN-γ at the 7th day with EM analysis. Conclusion;TNF-α and recombinant cytokines being similar to those produced by HIV- 1 infected T Cells could really induce HHV- 8 lytic cycle replication in BC-3 cells, another cell line of PEL.

Human herpesvirus 6A induces apoptosis of HSB-2 cellsvia a mitochondrion-related caspase pathway

Apoptosis plays an important role in the pathogenesis of viral infections.In this study,we investigated the cell death processes during productive HHV-6A infection and the underlying mechanisms.Annexin V-PI staining and electron microscopy indicated that HHV-6A is a strong inducer of apoptosis.HHV-6A infection decreased mitochondrial transmembrane potential and led to morphological changes of mitochondria.The cell death was associated with activation of caspase-3 and cleavage of DNA repair enzyme poly （ADP-ribose） polymerase,which is known to be an important substrate for activated caspase-3.Caspase-9 was activated significantly in HHV-6A-infected cells,whereas caspase-8 was not activated obviously.Moreover,HHV-6A infection upregulated Bax and downregulated Bcl-2.This is the first demonstration of mitochondrion-mediated,caspase-dependent apoptosis in HHV-6A-infected cells.

Effectof the Local Strain CN5 of Human Herpesvirus 6 on CD Molecule Expression and PHA-Induced Proliferation of Cord Blood or Peripheral Blood Mononuclear Cells

Cord blood mononuclear cells (CBMC's) and adult peripheral blood mononuclear cells (PBMCs), cultured with RPMI 1640 medium containing 20% fetal calf serum plus 5 mg/L PHA and 10 mg/L IL-Z, were inoculated with CN5 strain of human herpesvirus 6 (HHV 6 ) isolated from a Chinese patient with exanthem subitum and the CN5 infected cell lysates were added to cultures of CBMCs and PBMCs, so as to observe the effects of the local strain CN5 on expression of CD molecule or on proliferation of mononuclear cells by the methods of APAAP staining and MTT assay.The results were as follows: ①Expressions of some CD antigens of CBMCs and PBMCs could change after CN5 strain infection. In both cases, CD3 expresion was down-regulated while CD4 expression was up-regulated. There were no significant differences of CD2, CD8 and CD45RA expressions between the two groups with and without CN5 infection. But the ratio of CD4 to CD8 sigmificantly rose because of the increasing of CD4 positiveity. ②The lysates of CB5-infected CBMCs inhibited the liferation of PBMCs, not of CBMCs, in a protein concentration-dependent pattern. This inhibition was partially neutralized by specific antiserum to CN5, not by antisera to INF-α and TNF-α.

A Novel 2-dimensional Multiplex qPCR Assay for Single-Tube Detection of Nine Human Herpesviruses

Human herpesviruses are double-stranded DNA viruses that are classified into nine species.More than 90%of adults are ever infected with one or more herpesviruses.The symptoms of infection with different herpesviruses are diverse ranging from mild or asymptomatic infections to deadly diseases such as aggressive lymphomas and sarcomas.Timely and accurate detection of herpesvirus infection is critical for clinical management and treatment.In this study,we established a single-tube nonuple qPCR assay for detection of all nine herpesviruses using a 2-D multiplex qPCR method with a house-keeping gene as the internal control.The novel assay can detect and distinguish different herpesviruses with 30 to 300 copies per 25µL single-tube reaction,and does not cross-react with 20 other human viruses,including DNA and RNA viruses.The robustness of the novel assay was evaluated using 170 clinical samples.The novel assay showed a high consistency(100%)with the single qPCR assay for HHVs detection.The features of simple,rapid,high sensitivity,specificity,and low cost make this assay a high potential to be widely used in clinical diagnosis and patient treatment.

Partial Sequence Analysis of the Genome of Human Herpesvirus 7 YY5 Isolated from Saliva Samples

Objective To isolate and identify Nanjing local strains of Human Herpesvirus 7 (HHV 7), and to analyze their partial genome characteristic. Methods The saliva specimens were collected from 2 healthy adults and 5 children with kidney disease. After treatment with antibiotics and filtering. they were inoculated on to the phytohemagglutin stimulated umbilical cord blood mononuclear cells (CBMCs). When the infected cells presented the typical ballooning and polykaryotic cytopathic effects (CPE), we identified them by transmission electron microscopy and polymerase chain reaction. PCR product was also sequenced. Results Four strains were isolated from the seven saliva specimens. The 186 base pair fragment of the isolated strain YY5 PCR products was sequenced, which encoded part of the HHV 7 U10 gene. The DNA sequence revealed an identity of 57.5% and 36 0%, respectively with HHV 6 and human cytomegalovirus (HCMV). At the amino acid level, the similarity of 51.6% was found between HHV 7 and HHV 6, and that of 25.8% between HHV 7 and HCMV. Conclusion The isolated viruses were HHV 7, and 186 bp fragments revealed an identity with HHV 7 RK and JI of 100%.

Primary Effusion Lymphoma in a HIV-1/2-Infected Patient

Background: Primary effusion lymphoma (PEL) is a lymphoid proliferation related to Kaposi sarcoma herpesvirus 8/human herpesvirus 8 (KSHV/HHV8) that affects mainly human immunodeficiency virus (HIV) infected individuals but can also occur in other immunodeficiency settings. It is characterized by lymphomatous effusions in different serous body cavities without the presence of a detectable tumor mass. The diagnosis is challenging and the clinical outcomes are poor. Aim: The aim of this paper is to report a rare case of PEL in a man who have sex with women (MSW) with HIV-1/2 infection, history of visceral Kaposi sarcoma (KS) and the development of a seronegative arthritis previous to the lymphoproliferative disease diagnosis. PEL presented with ascites, was treated with high-dose chemotherapy and autologous stem cell transplantation, with a good clinical outcome. Case Presentation: We describe a case of a 48-year-old HIV-1/2-infected patient from a high HHV8 seroprevalent country, hospitalized following a three-month history of increased abdominal volume and general constitutional symptoms. Laboratory data revealed normocytic normochromic anemia and a high level of lactate dehydrogenase. A diagnostic paracentesis was performed with cytology compatible with high-grade B-cell lymphoma. Peritoneal fluid cytology showed large lymphoid cells expressing leucocyte-common antigen CD45 without expression of the CD20 antigen (B-lymphocytes) and positivity for HHV8 by immunocytochemical staining, compatible with the diagnosis of PEL.

Pityriasis Rosea-Like Eruption by Covid-19 Infection: A New Case Report

Background: Coronavirus disease (Covid-19) becomes a pandemic worldwide in 2020. Different dermatological manifestations associated with Covid-19 infection like maculopapular, morbilliform, urticarial, vesicular, chilblain-like, petechiae, purpura, and livedoid rashes. Pityriasis rosea (PR) and PR-like eruptions were recently reported to increase in coronavirus cases. Aim: To evaluate and review the literature on PR and PR-like eruption associated with Covid-19 disease. Case Report: A 24-year-old female patient presented with a history of asymptomatic PR-like eruption that started during infection with the Covid-19 virus and resolved spontaneously over 14 weeks without therapy. Conclusion: PR and PR-like eruptions are not uncommon with Covid-19 disease and could be the early manifestation of SARS-CoV-2 virus infection.

Isolated ileal perforation due to cytomegalovirus reactivation during management of terbinafine hypersensitivity

We report a case of 71-year-old man who developed a hypersensitivity syndrome associated with terbinafine. He was placed on terbinafine (250 mg/d) for the treatment of tinea pedis due to diabetes mellitus. Following the treatment with terbinafine, he developed druginduced hypersensitivity syndrome (DIHS). Systemic corticosteroid led to transient improvement of his clinical manifestations. Three months after disease onset, he presented with panperitonitis due to ileal perforation, and underwent an emergency operation. The affected ileum was resected and ileostomy was performed in the terminal ileum. Cytomegalovirus (CMV)-specific IgG antibodies were significantly increased, high-titer CMV antigenemia was detected, and pathological examination of the resected ileum confirmed CMV infection. Based onthese observations, we strongly recommend that physicians monitor reactivation of the family of herpesvirus other than herpesvirus 6, to manage DIHS properly.

Effects of HHV-6 Infection in Vitro on Cytokines Induction and NK Activity of Peripherial Blood Mononuclear Cells

Three Nanjing local strains (CN5, CN8, CN10) of human herpesvirus 6 (HHV-6] had been isolated and identified by electronmicroscopy, antibody reactions with IFA and specific PCR. The purpose of this paper was to study effects on cytokines synthesis and NK activity of peripheral blood mononuclear cells(PBMC) in vitro post infection of human herpesvirus 6. PBMCs cultural supernatants were collected at different hours post infection. Cytokines such as TNF-α, IFN-α and IL-8 could be detected as early as 24 h post infection, plateaued at 48h, and then decreased gradually. The levels of these cytokines in infected PBMCs supernatants were markedly higher than those in uninfected ones, but the IL-6 level was lower than that of uninfected one. These differences between infected and uninfected groups were all significant(P<0.05). There were no differences in the induction of TNF-α, IFN-α and IL-8 between the local strain CN8 and GS strain (all P>0.05), while the inhibition of IL-6 production induced by GS strain was more prominant than that induced by CN8 (P<0.05). It was also found that NK activity was augmented at 24h post infection, which was more striking in CN8 strain infection group than in GS strain infection group (P<0.05), after then, it was gradually decreased. From these reults, it could be inferred that the increase of cytokines synthesis and augmentation of NK activity were associated with convalescence and pathogenicity of the HHV-6 infection. GS strain, which belongs to groups A, disturbed the function of human immunity more remarkably than the local strain CN8, which belongs to group B.

荧光定量PCR检测献血人员外周血白细胞中人疱疹病毒DNA

目的调查献血人员外周血白细胞中8种人疱疹病毒的DNA分布情况,为我国献血者健康标准要求的完善提供参考性实验数据。方法收集献血人员外周血标本427例,分离外周血白细胞后提取DNA,使用Taqman探针法荧光定量PCR检测方法对8种疱疹病毒DNA的阳性率和病毒载量进行检测。结果 427例标本中未检测到单纯疱疹病毒1型(HSV1)、HSV2、水痘-带状疱疹病毒(VZV)和人疱疹病毒8型(HHV-8)的DNA,EB病毒(EBV)、人巨细胞病毒(HCMV)、HHV-6、HHV-7阳性率分别为51.4%、6.5%、50.6%、21.1%,其中HCMV、EBV和HHV-6均阳性的标本占6.5%,EBV和HHV-6均阳性的标本占25.1%,EBV与HHV-7均阳性的标本占4.0%,HHV-6和HHV-7均阳性的标本占6.9%。EBV、HCMV、HHV-6、HHV-7的病毒载量中位数分别为559、336、4 683、1 126 gqe/ml外周血。在不同性别和年龄组中EBV、HHV-6和HHV-7在三个年龄组中的检出率差异无统计学意义,但CMV的检出率随年龄的增加逐渐升高,差异有统计学意义(P<0.05)。市区与郊区人群相比EBV、HCMV、HHV-6和HHV-7的检出率均显著较低(OR=0.657、0.798、0.889、0.721,95%CI:0.147~2.451、0.224~2.196、0.221~2.703、0.194~2.445,P<0.05)。结论在献血人员外周血白细胞中可以检出多种疱疹病毒DNA,提示我国献血者健康标准要适时考虑献血者疱疹病毒感染的情况。

检测7种疱疹病毒的基因芯片法及其初步应用

目的建立一种快速分型检测临床常见的7种疱疹病毒的新方法。方法以7种人疱疹病毒的DNA多聚酶基因区为靶序列,设计多重引物及寡核苷酸分型探针,点样制成基因芯片。用所建基因芯片检测282份疑似病毒感染患儿血标本,以荧光定量PCR法作对照,评价该芯片的诊断价值。结果基因芯片法最低检出浓度为10拷贝/μl,HBV、金黄色葡萄球菌、大肠埃希菌、白色念珠菌及人基因组DNA等无杂交信号。282份血标本共检出阳性59份,以荧光定量PCR法检测结果为标准,其敏感性为96.7%,特异性为99.5%,Youden指数为0.962;两法总符合率98.9%。结论研制的基因芯片可同时检测7种人疱疹病毒,且特异敏感、快速简便,有临床应用价值。

人类免疫缺陷病毒/丙型肝炎病毒及人类免疫缺陷病毒/人类疱疹病毒合并感染的流行现状

在抗逆转录病毒治疗时代,人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者(people livingwithHIV,PLWH)的主要发病及死亡原因是机会性感染。全球现存活的PLWH中,约6.2%的病例合并感染了丙型肝炎病毒(hepatitis C virus,HCV),而几乎所有病例至少合并感染了1种人类疱疹病毒(human herpesvirus,HHV)。因全球检测和治疗覆盖率不足,且受社会经济不平等、医疗资源分配不均和政策限制等的严重影响,HIV的机会性感染已成为全球艾滋病领域最关注的公共卫生问题之一。本文综述了HIV/HCV及HIV/HHVs合并感染的流行现状,并总结了相应的防控策略,以期为防控HIV的机会性感染提供参考。

三株人鼻咽癌Scid小鼠移植瘤的建立及特性研究

目的 建立鼻咽癌鼠移植瘤 ,为鼻咽癌的特异性免疫治疗研究提供实验模型。方法 从 2 6例未治的鼻咽癌病人鼻咽部铰取肿瘤组织 ,分别皮下接种BALB c裸小鼠 (14只 )和Scid小鼠 (12只 ) ;成功建立移植瘤株后观察其生长特性、形态、染色体和LMP的表达情况。结果 成功建立鼻咽癌Scid小鼠移植瘤株CSNET 1、CSNET 2和CSNET 3,已分别传至第 11代 (2 3个月 )、第 14代 (17个月 )和第 9代 (16个月 ) ,其光镜和电镜下形态符合低分化鳞癌的特征 ,电镜下在CSNET 1中可观察到Ep stein Barr病毒样颗粒 ,CSNET 1的染色体全部为人体细胞来源的染色体 ,免疫组化检测结果 ,3个瘤株均可见EB病毒晚期膜蛋白LMP 1和LMP 2阳性细胞。结论 CSNET 1、CSNET 2和CSNET 3是人类来源的鼠移植瘤株 。

Epstein-Barr病毒bhrfl表达对鼻咽癌细胞株CNE2拓扑异构酶Ⅰ表达的影响

目的 了解Epstein Barr(EB)病毒基因bhrfl表达对鼻咽癌细胞拓扑异构酶Ⅰ表达的影响。方法 通过构建bhrfl表达载体并转染鼻咽癌细胞株CNE2细胞 ,以检测癌细胞在转染后其拓扑异构酶Ⅰ表达及其抗喜树碱诱发凋亡能力的改变。结果 bhrfl表达可增强癌细胞拓扑异构酶Ⅰ的表达 ,使癌细胞对喜树碱的敏感性下降 ,生存时间延长 ,凋亡率减少 (P <0 0 1)。结论 bhrfl的表达可通过增强CNE2细胞拓扑异构酶Ⅰ的表达而增强其抗喜树碱诱发的细胞凋亡作用。

EB病毒编码潜伏膜蛋白－1与鼻咽癌免疫治疗

综述近年来EB病毒（Epstein—Barrin virus）编码的潜伏膜蛋白1（Iatent membrane protein，LMP－1）对鼻咽癌（nasopharyngeal carcinoma，NPC）患者免疫系统影响和对其进行免疫治疗方面的研究进展情况，并着重介绍针对潜伏膜蛋白1的免疫治疗研究现状。

疱疹病毒感染与特发性肺纤维化关系的分子生物学证据

目的探讨疱疹病毒感染和特发性肺纤维化(IPF)的关系。方法采用体外基因扩增技术检测33例IPF患者(25例散发性和8例家族性)与25例对照组患者的肺组织人疱疹病毒及JC、BK病毒核酸,并经免疫组织化学、电镜检查及试验性治疗进一步确认。结果IPF患者肺组织中巨细胞病毒、Epstein-Barr病毒以及人疱疹病毒8型的检出率显著高于对照肺组织,IPF患者肺组织检查到EBV和HHV-8病毒特异性抗原、直径近似于疱疹病毒的病毒样颗粒。IPF患者肺功能试验性治疗后获得改善。结论疱疹病毒感染是IPF发生发展过程中重要的触发因子。