醫(yī)學(xué)微生物學(xué)課件：皰疹病毒

1、Herpesvirus皰疹病毒 結(jié)構(gòu)相似：有包膜,中等大小,球形, 基因組： dsDNA 病毒 100多種，分 /三個(gè)亞科Classification皰疹病毒家族3亞 科常用名英文縮寫皰疹病毒單純性皰疹病毒1型HSV-1單純性皰疹病毒2型HSV-2水痘-帶狀皰疹病毒VZV皰疹病毒人巨細(xì)胞病毒HCMV人皰疹病毒6型HHV-6人皰疹病毒7型HHV-7皰疹病毒EB病毒EBV卡波西肉瘤相關(guān)皰疹病毒HHV-8Classification 亞科 種類 宿主范圍 復(fù)制 CPEalpha： HHV1-3 較廣 較快 +beta： HCMV 較窄 緩慢 + HHV6-7gamma：EB病毒 窄 潛伏 + HHV

2、8 皰疹病毒的共同特點(diǎn)結(jié)構(gòu)相似：包膜/中等大小/球形, 衣殼20面體對(duì)稱基因組： 200-240kb（200 proteins）二倍體細(xì)胞內(nèi)增殖，核內(nèi)復(fù)制，CPE明顯：嗜酸性包涵體，多核巨細(xì)胞。感染類型多樣：溶細(xì)胞感染潛伏感染為其主要特點(diǎn)先天感染先天畸形整合感染與致癌有關(guān)Important properties IThe HSV envelope contains at least 8 glycoproteins. The matrix or tegument （皮層）which contacts both the envelope and the capsid contains at lea

3、st 15-20 proteins. 包膜： 8種糖蛋白 皮層：15-20種蛋白質(zhì)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 基因組：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）：啟動(dòng)病毒復(fù)制 早期蛋白：病毒復(fù)制的相關(guān)酶類 （pp65） 晚期蛋白：病毒的結(jié)構(gòu)蛋白 潛伏性感染 ：潛伏相關(guān)轉(zhuǎn)錄體 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 感染類型多樣Apparent （顯性感染，primary）latent infect

8、ion (隱伏感染) 激活與復(fù)發(fā)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(宮頸) carcinomaGlioma（神經(jīng)膠質(zhì)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) (單純皰疹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隱伏:三叉/頸上/迷走神經(jīng)節(jié) （ trigeminal ganglion ）引起：口唇皰疹 （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 （齦口炎）HSV-2Latent : the sacral ganglion (骶神經(jīng)節(jié))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(齦口炎)+-Herpes encephalitis+-Keratoconjunctivitis(角膜結(jié)膜炎)+-cold sores (唇皰疹)+-Genital herpes+ mostNeonatal infection（新生兒感染）+cervical carcinoma-+Overview of Herpesvirus

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

15、根神經(jīng)節(jié)chickenpoxShingles Latent:Dorsal root ganglia Cranial (顱) 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) (單純皰疹v.)HSV-lip/month/genital herps/cervical carcinomavaricella zoster virus(水痘帶狀皰疹v.)VZV-chicken pox/zoster (shi

17、ngles)Human cytomegalovirus (巨細(xì)胞 v.)HCMV- congenital malformations（先天畸形） and death /cancer/移植排斥Human Cytomegalovirus (HCMV)1956年首次分離1960年命名為巨細(xì)胞病毒1973年正式命名為HHV-5人群普遍感染90% 先天感染致畸，成人免疫力低下時(shí)感染亞科, dsDNA（230kb），皰疹病毒中基因組最大。巨細(xì)胞病毒（Cytomegalovirus，CMV）Human Cytomegalovirus (HCMV)Latent :Salivary gland (唾液腺）/ki

18、dney/monocyte-MDiseases:Vertical-Congenital and perinatal(圍產(chǎn)期) infections: 癲癇/先天畸形（耳聾）Horizontal transmissionSpontaneous infectious mononucleosis-like syndrome (傳染性單核增多樣綜合征)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) (單純皰疹v.)HSV-lip/month/genital herps/cervical carcinomavaricella zoster virus(水痘帶狀皰疹v.)VZV-c

21、hiken pox/zoster(shingles)cytomegalovirus (巨細(xì)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年首次分離1983年完成原型株（B95.8株）全基因組測序嗜B淋巴細(xì)胞，與多種疾病有關(guān)腫瘤病毒不能常規(guī)體外培養(yǎng)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（單核細(xì)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) (單純皰疹v.)HSV-lip/month/genital herps/cervical carcinomavaricella zoster virus (VZV)-chiken pox /zoster (shingles)cytomegalovirus (巨細(xì)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 (人類皰疹v.)Herpes B virus(皰疹B v.)Human herpesvirus 6, 7, 8(人類皰疹v.)Human herpesvirus 6Was first recognized in 1986exanthum subitum(幼兒急疹) /roseola infantum (嬰兒玫瑰疹) Human herpesvirus 7First isolated in 1990exanthum subitum(幼兒急疹)/hepatitis / encephalitisHuman herpesvirus 8 was first detected in 1994 in

26、 Kaposis sarcoma specimens人皰疹病毒6、7、8（Human herpes virus，HHV 6, 7, 8）HHV-6：1986年分離，幼兒急疹/嬰兒玫瑰疹HHV-7：1990年分離，幼兒急疹/肝炎 / 腦炎HHV-8：1994年分離， Kaposis 肉瘤病人57NameTarget cellLatencyTransmissiondiseasesHSV-1MucoepitheliaNeuronClose contact唇皰疹等HSV-2MucoepitheliaNeuronClose contact usually sexual生殖器皰疹,新生兒皰疹，宮頸caVZ

27、VMucoepitheliaNeuronContact or respiratory route水痘，帶狀皰疹EBVB cell, epitheliaB cellSaliva鼻咽Ca，BL傳染性單核細(xì)胞增多癥HCMVEpithelia, monocytes, lymphocytesMonocytes, lymphocytes and possibly othersContact, blood transfusions, transplantation, congenital輸血后單核細(xì)胞增多癥輸血后肝炎,宮頸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