医学微生物学课件：疱疹病毒

1、Herpesvirus疱疹病毒 结构相似：有包膜,中等大小,球形, 基因组： dsDNA 病毒 100多种，分 /三个亚科Classification疱疹病毒家族3亚 科常用名英文缩写疱疹病毒单纯性疱疹病毒1型HSV-1单纯性疱疹病毒2型HSV-2水痘-带状疱疹病毒VZV疱疹病毒人巨细胞病毒HCMV人疱疹病毒6型HHV-6人疱疹病毒7型HHV-7疱疹病毒EB病毒EBV卡波西肉瘤相关疱疹病毒HHV-8Classification 亚科 种类 宿主范围 复制 CPEalpha： HHV1-3 较广 较快 +beta： HCMV 较窄 缓慢 + HHV6-7gamma：EB病毒 窄 潜伏 + HHV

2、8 疱疹病毒的共同特点结构相似：包膜/中等大小/球形, 衣壳20面体对称基因组： 200-240kb（200 proteins）二倍体细胞内增殖，核内复制，CPE明显：嗜酸性包涵体，多核巨细胞。感染类型多样：溶细胞感染潜伏感染为其主要特点先天感染先天畸形整合感染与致癌有关Important properties IThe HSV envelope contains at least 8 glycoproteins. The matrix or tegument （皮层）which contacts both the envelope and the capsid contains at lea

3、st 15-20 proteins. 包膜： 8种糖蛋白 皮层：15-20种蛋白质HSV . When the envelope breaks and collapses away from the capsid, negatively stained virions have a typical fried-egg appearance Important properties IIdsDNA v. , enveloped, 150200nmReplication in the nucleus 基因组：Very complex Large with different size （71-20

4、8 genes，encoding 67-197 proteins） complex structure complex replication cycle Replicative cycleBinding with receptors, fusion and uncoatingReplication 即刻早期蛋白（IE-protein）：启动病毒复制 早期蛋白：病毒复制的相关酶类 （pp65） 晚期蛋白：病毒的结构蛋白 潜伏性感染 ：潜伏相关转录体 增殖型感染 ：IE-proteindsDNA v. , enveloped, 150200nmReplication in nuclear CPE

5、, acidophilic intranuclear inclusions Important properties IIIHerpes simplex 1: Histological stain. Note the multinucleate cell with dark staining inclusions.inclusions Nuclei of infected cells become enlarged eosinophilic intra-nuclear inclusions.The nuclei become distorted and contain eosinophilic

6、 inclusions. Other manifestations of CPE include the formation of giant cells, and also multi-nucleate syncytia (most common with HSV type 2)H&E stain of lung section showing nuclear inclusions with the appearance of an owls eye. The inclusion is surrounded by a clear halo that extends to the nuclea

7、r membrane. CMV infection can occur without the typical cytomegalic cells. Important properties IVdsDNA v. , enveloped, 150200nmReplication in nucleus CPE, acidophilic intranuclear inclusions Infectious types varies- latent infection Varied infectious types 感染类型多样Apparent （显性感染，primary）latent infect

8、ion (隐伏感染) 激活与复发Congenital (先天性感染)Integration (整合感染) Herpesviruses are linked with malignant tumors Vertical congenital infection/fetus abnormality Important properties VdsDNA v. , enveloped, 150200nmReplication in nuclear CPE, acidophilic intranuclear inclusions Infectious types varies- latent infe

9、ctionHerpesviruses are linked with malignant diseases in human and lower animalsHCMV、HSV-2 Cervical(宫颈) carcinomaGlioma（神经胶质瘤）EBV Burkitts lymphoma of African children nosopharyngeal carcinoma(鼻咽ca)other lymphomas Important properties VIdsDNA v. , enveloped, 150200nmReplication in nuclear CPE, acido

10、philic intranuclear inclusions Infectious types varies- latent infectionHerpsviruses have been linked with malignant diseases in human and lower animalsVertical congenital infection/ fetus abnormality Overview of Herpsvirus Diseasesherpes simplex virus (types 1 and 2) (单纯疱疹v.)HSV-lip/month/Genital h

11、erps/ cervical carcinomaSites at which HSV-1 and HSV-2 cause diseases HSV-1 sero-prevalence by age and time period26J Infect Dis. 2014 Feb;209(3):325-33.HSV-1隐伏:三叉/颈上/迷走神经节 （ trigeminal ganglion ）引起：口唇疱疹 （Cold sore）Cold soreHSV can set up a primary infection in the lips, move to the trigeminal gangl

12、ion where it can remain latent. Virus can subsequently reactivate, move to the original site of infection and result in cold sores Gingivostomatitis （龈口炎）HSV-2Latent : the sacral ganglion (骶神经节)Disease :Genital herpesHSV-2 sero-prevalence by age and time period31J Infect Dis. 2014 Feb;209(3):325-33.

13、HSV-1HSV-2transmissionContact sexualSite of latencyTrigeminal gangliaSacral gangliaPrimary infection+ 90% subclinical+Gingivostomatitis(龈口炎)+-Herpes encephalitis+-Keratoconjunctivitis(角膜结膜炎)+-cold sores (唇疱疹)+-Genital herpes+ mostNeonatal infection（新生儿感染）+cervical carcinoma-+Overview of Herpesvirus

14、Diseases herpes simplex virus (types 1 and 2)HSV-lip/month/genital herpes/cervical carcinomavaricella zoster virus(水痘带状疱疹v.)VZV-chicken pox/zoster (shingles)Transmission electron micrograph of varicella- zoster virions from vesicle fluid of patient with chickenpox Varicella Zoster Virus (水痘带状疱疹v)脊髓后

15、根神经节chickenpoxShingles Latent:Dorsal root ganglia Cranial (颅) nerve ganglia Zoster(Shingles)Typical isolated rash in shinglesThis is a classic case of chickenpox of the newborn. The infant contracted chickenpox at birth from her infected mother. A severe skin infection has developed on the face and

16、neck and, without treatment, this infection could spread throughout the body and cause serious illness or even death. Overview of Herpesvirus Diseasesherpes simplex virus (types 1 and 2) (单纯疱疹v.)HSV-lip/month/genital herps/cervical carcinomavaricella zoster virus(水痘带状疱疹v.)VZV-chicken pox/zoster (shi

17、ngles)Human cytomegalovirus (巨细胞 v.)HCMV- congenital malformations（先天畸形） and death /cancer/移植排斥Human Cytomegalovirus (HCMV)1956年首次分离1960年命名为巨细胞病毒1973年正式命名为HHV-5人群普遍感染90% 先天感染致畸，成人免疫力低下时感染亚科, dsDNA（230kb），疱疹病毒中基因组最大。巨细胞病毒（Cytomegalovirus，CMV）Human Cytomegalovirus (HCMV)Latent :Salivary gland (唾液腺）/ki

18、dney/monocyte-MDiseases:Vertical-Congenital and perinatal(围产期) infections: 癫痫/先天畸形（耳聋）Horizontal transmissionSpontaneous infectious mononucleosis-like syndrome (传染性单核增多样综合征)Subclinical hepatitisCancer：Cervical carcinoma/ gliomaRetrieved at /pmc/articles/PMC1656547/HCMV Infection at Different Age Gro

19、ups HCMV in MaleHCMV in Female HCMV infection prevalence increases with age HCMV in the brain sections in RE patients6366-HCMV-400X+3226-HCMV-400X+4207-HCMV-400X-0074-HCMV-400X+ACBDImmunohistochemical staining of HCMV pp65 in brain sections. No pp65 is detected in control tissue (A) and pp65 immunor

20、eactivity is observed in a grade II oligoastrocytoma (B), a grade III Anaplastic astrocytoma(C) and a grade Glioblastoma multiforme (D). 400.Overview of Herpsvirus Diseasesherpes simplex virus (types 1 and 2) (单纯疱疹v.)HSV-lip/month/genital herps/cervical carcinomavaricella zoster virus(水痘带状疱疹v.)VZV-c

21、hiken pox/zoster(shingles)cytomegalovirus (巨细胞v.)CMV-congenital malformations and death /cervical carcinomaEpstein-Barr virus(EB v.)EBV- nasophyaryngeal carcinoma (鼻咽ca)/Burkitts lymphomaEpstein-Barr virus(EBV)1964年首次分离1983年完成原型株（B95.8株）全基因组测序嗜B淋巴细胞，与多种疾病有关肿瘤病毒不能常规体外培养Epstein-Barr virus(EBV)Latent :

22、B cellCells: The virus only infects a small number of cell types that express the receptor for complement C3d component (CR2 or CD21). certain epithelial cells (naso-pharynx) B lymphocytesDiseases:infectious mononucleosis（单核细胞）nasophyaryngeal carcinoma （鼻咽癌）Burkitts lymphoma (BL)Hodgkins diseaseBurk

23、itts Lymphoma H&E stain of lung section showing nuclear inclusions with the appearance of an owls eye. The inclusion is surrounded by a clear halo that extends to the nuclear membrane. CMV infection can occur without the typical cytomegalic cells. Overview of Herpsvirus Diseasesherpes simplex virus

24、(types 1 and 2) (单纯疱疹v.)HSV-lip/month/genital herps/cervical carcinomavaricella zoster virus (VZV)-chiken pox /zoster (shingles)cytomegalovirus (巨细胞v.)CMV-congenital malformations and death /cancerEpstein-Barr virus (EB v.)EBV- nasophyaryngeal carcinoma (鼻咽ca)/Burkitts lymphomaHuman herpesvirus 6, 7

25、, 8 (人类疱疹v.)Herpes B virus(疱疹B v.)Human herpesvirus 6, 7, 8(人类疱疹v.)Human herpesvirus 6Was first recognized in 1986exanthum subitum(幼儿急疹) /roseola infantum (婴儿玫瑰疹) Human herpesvirus 7First isolated in 1990exanthum subitum(幼儿急疹)/hepatitis / encephalitisHuman herpesvirus 8 was first detected in 1994 in

26、 Kaposis sarcoma specimens人疱疹病毒6、7、8（Human herpes virus，HHV 6, 7, 8）HHV-6：1986年分离，幼儿急疹/婴儿玫瑰疹HHV-7：1990年分离，幼儿急疹/肝炎 / 脑炎HHV-8：1994年分离， Kaposis 肉瘤病人57NameTarget cellLatencyTransmissiondiseasesHSV-1MucoepitheliaNeuronClose contact唇疱疹等HSV-2MucoepitheliaNeuronClose contact usually sexual生殖器疱疹,新生儿疱疹，宫颈caVZ

27、VMucoepitheliaNeuronContact or respiratory route水痘，带状疱疹EBVB cell, epitheliaB cellSaliva鼻咽Ca，BL传染性单核细胞增多症HCMVEpithelia, monocytes, lymphocytesMonocytes, lymphocytes and possibly othersContact, blood transfusions, transplantation, congenital输血后单核细胞增多症输血后肝炎,宫颈caBrief SummaryNameTarget cellLatencyTransm

28、issionHerpes simplex-1 (HSV-1)MucoepitheliaNeuronClose contactHerpes simplex-2 (HSV-2)MucoepitheliaNeuronClose contact usually sexualVaricella Zoster virus (VSV)MucoepitheliaNeuronContact or respiratory routeEpstein-Barr Virus (EBV)B lymphocyte, epitheliaB cellSalivaCytomegalovirus (CMV)Epithelia, monocytes, lymphocytesMonocytes, lymphocytes and possibly othersContact, blood transfusions, transplantation, congenitalBrief SummaryKey WordsHerpesvirusacidophilic