病原微生物13疱疹病毒

1、Hes comesfrom Greek word“hein”（tocreep or crawl）HesesDongli PanDepartment of Medical Microbiology and ParasitologyUniversity School of Medicine 2016.10panClassificationHesviridaeAlphah科esvirinae亚科HSV-1 HSV-2 VZV. (animales)Betahesvirinae HCMV HHV-6 HHV-7.(animales)GammahesvirinaeEBV KSHV.(animales)T

2、here are 8 currently known human hesesCommon features1.Shand structure：spherical, 120-260 nmmeter, dsDNA genome (124-295kb，encoding 70-200 proteins） is linearhe viral particute衣circularizedhe nuclei of infected cells；Capsids have icosahedral （20面体）symmetry. There is a tegument （皮层） and an envelope (

3、包膜）。包膜糖蛋白包膜线性dsDNA皮层衣壳潜伏复发整合Biological Cycle of Heses(Including congenital infection)Primary Infection建立潜伏Establish latency增殖染（裂解）潜伏Latent infectionProductive (lytic) infection激活Recurrent Infection复发Human hesesSubfamilySpeciesPrimary CellSite of LatencyMeans of SpreadDiseases口唇疱疹齿龈炎HSV-1 (HHV-1)Neur

4、onClose contactCold sores, gingivostomatitisMucothelial cellsH疱疹性角膜炎脑炎HSV-2 (HHV-2)Mucothelial cellsNeuronClose contact( sexual transmis)Genital hes疱疹水痘带状疱疹hesvirinaeVZV (HHV-3)NeuronRespiratory and close contactChicken pox, Shingles单核细胞增多症 视网膜炎MucollshesvirinaeHCMV (HHV-5)Monocyte, lymphocyte, andt

5、helial cellsMonocyte, lymphocyte, and ?Close contact transfus, tietransplant, congenitalInfectious mononucleosis, Retinitis,Diseases for newborn andpromised新生儿和免疫低下者HHV-6T cells and ?T cells and ?Respiratory and close contactRoseola, Others?红疹HHV-7T cells and ?T cells and ?Roseola, Others?EBV (HHV-4

6、)B cellSaliva ( Kissing disease )Infectious mononucleosis, nasopharyngeal carcinoma,鼻咽癌Burkitts lymphoma malignant lymphomaB cell andthelialcellhesvirinaeKSHV (HHV-8)Lymphocyte and other cellB cellClose contact (sexual), saliva?Kaisa卡波西肉瘤HesviridaeHes Simplex(HSV)HSV-1 (HHV-1)HSV-2 (HHV-2)Biological

7、 propertiesSpherical, 120-150 nm, 150 kb dsDNAHSV-1 and HSV-2 are 50% homologousCan be easily propagatedany cell lines (most commonly Vero cells)Form visible plaques, multinucleated giant cells and Cowdry type 1incluAnimal mbodies (acidophilic nuclear inclus: mouse, rabbit, Guinea pig.bodies)Plaquem

8、ultinucleate cell with darkstaining inclusReplication cycleDiseases caused by HSVHSV-2HSV-1Cold sores口唇疱疹疱疹Genital hHSV-1 too)es, can be caused by齿龈炎etic gingivostomatitisH脑膜炎etic meningitis角膜炎etic keratitisHHNeonatal hes疱疹性脑炎Hes simplex encephalitis(70% fatality rate)新生儿疱疹Neonatal hesPathogenesisPr

9、imary infectionTransmiscytolysisby direct touch or sex (HSV-2 mostly by sex) Blistershe skin水疱Congenital infectionMother to baby transmis胎盘through placentaLatent infectionlatently infected ganglia in a non-replicating eHSV-1, trigeminal ganglia(三叉神经节);HSV-2, sacral ganglia(骶神经节)sReactivation and rec

10、urrent infectionTriggers: fever, emotional stress, fatigue,menstruation, immunosuppres, etc.Thestarts to replicate and travels back toperipheral ties, resulting in recurrent infection.Latency/reactivation cycles are with you LIFE TIME.HSV latency and reactivation on the cellular levelDiagnosisApproa

11、entTzanck test: Direct microscopic examination of cells from base of leMultinucleated giant cells and cowdry type A inclubodies.Cell culture (gold standd)Inoculate Vero, BHK-21 cells, etc. HSV replicates and cause identifiable cytopathic effects (CPE): see plaques.Assay of tismear, cerebrospinal flu

12、id, or vesicular fluid for HSV antigenenomeELISA, immunofluorescent stain, in situ hybridization and PCRSerologySpecific IgM indicates recent infectionTreatment and prevention阿昔洛韦Acyclovir (or similar nucleosideogs and their derivatives)Patients with genital hes should avoidercourse whenthey have th

13、e prodromal itching symptoms or an active le.No vaccine yet. HSV-2 vaccine is under-developmentNHNAcyclovir, a nucleosideog,NH2NNinhibits viral DNA polymeraseHO-CH2 OCH2CH2HesviridaeVaricella-Zoster水痘-带状疱疹(HHV-3)一毒两疾病！皆因可潜伏！Biological propertiesSimilar to HSVHas only 1 serotype Replicates in fibrobl

14、ast or cellsthelialForm multinucleated giant cells andCowdry type A incluHSVbodies, likeBut no working animal mChicken poxDroplets, direct contact主要通过飞沫Enter through respiratory system, conjunctiva or skin, etcSkins of whoodySecond ViremiaProliferate in local lymph nodeProliferate in mononuclear mac

15、rophageViremia血症Shingles俗称为:金蛇缠腰或缠腰龙Chicken pox as a childestablishes latencyin dorsal root ganglia or背根神经节trigeminal ganglia三叉神经节Replicate in skinTravel along Axons of sensory neuron to skinAfter adulthood, when stimulatedReactivatedVZV reactivation occurs more frequently in the elderlyA decline in

16、 VZV-specific T-cell levels may allow thepromiseds and into reactivateHost immunity may help maain latencyCongenital Varicella syndrome(性水痘综合征)Caused by infection in uteroduring thetrimesterLeads to scarring of the skin of the limbs, damage to the lens, retina and brainDiagnosis anderventionDiagnosi

17、sSymptoms are typical. Usually no need of lab tests.Tzanck test: Staining of sles scrd from the base of a vesicaland look for multinucleated giant cells, Cowdry type A inclu etc.TreatmentAcyclovirbodies,VaccineLive attenuated vaccineVZV-Ig for emergency prevention (like forpromisedVZV特异性免疫球蛋白patient

18、s)HesviridaeHuman cytomegalo(HCMV, HHV-5)Biological propertiesSpherical, 180-250 nm.成细胞HCMV only infects human cells. Fibroblast cells are used for propagation.It replicates slowly.猫头鹰眼状内涵体Infected cellse enlarged and form owls eye inclubodies (big嗜酸性核内内涵体acidophilic nuclear inclus with the appearan

19、ce of an “owls eyes”)is weak. Long term storage requires liquid nitrogen.H&E stain ofg sectionshowing owls eye inclusModes of transmisDirect contact: Sexual transmis hand to mouth, mouth to mouth,胎盘: transplacental,内rauterineVertical transmisinfection, cervical secretions, milk, saliva, etc宫颈物Medica

20、l procedures: Blood transfu,an graft60-90% of adults are seroitivees of HCMV infectionsInfection of healthy children and adultsUsually a lifelong and subclinical infectionPrimary infection can lead to infectious mononucleosisCongenital infectionHCMV infection is the leading cause of infectious conge

21、nital diseaseInfection of CNS can cause neurological abnormalities and deathNeonatal infectionreactivated during delivery Usually protected by mothers antibodiesInfection of immunosuppressed individualsTransplant recipients and AIDS patientsSevere complications including retinitis,视网膜炎Meningitis, p脑

22、膜炎onia, colonitis结肠炎HCMV retinitisDiagnosis anderventionLaboratory diagnosisCell culture qPCRTests of pp65 antigen in peripheral blood leukocytesSerology: ELISA for CMV-specific IgM indicateive infection,but may give false-itivesTreatment and preventionGanciclovir （更昔洛韦）Foscarnet（膦钾酸）No vaccine, but

23、 under developmentHesviridaeEpstein- Barr(HHV-4)Biological properties口咽Typical hesmorphology and structure.Cannot be grown in normal cell culture.Lytic infection of EBV usually occurs during primary infection oforopharyngealImportant lyticthelial cells or during reactivation from latency in B cells.

24、include: early antigen (EA), viral capsid antigen(VCA) and membrane antigen (MA)Latent infection mostly occurs in B cells. During latent infection limited viral are expressed. They include EB nuclear antigen (EBNA) andlatent membrane protein (LMP)Latent infection by EBV can transform and immortalized B cells, andoccaally resultsalignancies. EBNA-2, EBNA-3C and LMP-1are essential for transformation.PathogenesisTransmitted mainly by salivaReplication in oropharyngealthelial cellsInfects B cellshe local lymphatic syst