醫(yī)學(xué)微生物學(xué)資料：HIV Infection and Control

1、HIV Infection and Control Proportion of different infectious disease cases 1965-1995 (%)Transmitted by sex or bloodRespiratoryGastrointestinalVector-borne and natural endemicYearHuman Immunodeficiency VirusClassification of the virusRetroviridae family, lentivirusesLentiviruses from humans: HIV1, HI

2、V2, HTLVLentiviruses from nonhuman primates: SIVLentiviruses from nonprimates: FIV, BIV, EIA Important properties of lentiviruseViron: 80-100 nm spherical particlesGenome: Single-stranded RNA, positive sense and diploid genomeProteins: Envelope glycoproteins,reverse transcriptase,protease Human Immu

3、nodeficiency VirusClassification of the virusRetroviridae family, lentivirusesLentiviruses from humans: HIV1, HIV2, HTLVLentiviruses from nonhuman primates: SIVLentiviruses from nonprimates: FIV, BIV, EIA Story of HIVAIDS is a cross-species infections by simian viruses in rural Africa. I may take ma

4、ny years to complete the transmission.Social, economic and behavioral changes in the mid 20th century provided circumstances that allow HIV infection expandHIV is completely inactivated by all routinely used chemical disinfectants and physical methods.Infectivity of the virus disappears in 10 minute

5、s of room temperatureInfection dosage of HIV is 1000 times higher than that of HBVStory of HIVHIV模型圖脂雙層膜gp120gp41包膜糖蛋白p24衣殼蛋白p17內(nèi)膜蛋白p7核衣殼蛋白逆轉(zhuǎn)錄酶蛋白酶整合酶基因組全長9.2KB兩端含長末端重復(fù)序列（LTR）3個(gè)結(jié)構(gòu)基因（env、pol、gag）6個(gè)調(diào)節(jié)基因（tat、rev、nef、vif、vpr和vpu）Strucutre GenesGeneEncoded ProteinFunction of ProteingagP24, p7Nucleocapsidp

6、17MatrixpolReverse transcriptaseTranscribes RNA genome into DNAProteaseCleaves precusor polypeptidesIntegraseIntegrates viral DNA into host cell DNAenvgp120Attachment to CD40 proteingp41Fusion with host cellRegulatory Genesvif viral infectivity factortat transactivating proteinvpu viral protein Urev

7、 regulator of virion protein expressionnef negative regulatory factorRegulatory Genes Found in HIV That Are Required for ReplicationGeneProteinProtein Function tatTatActivation of transcription of viral genesrevRevTransport of late mRNA from nucleus to cytoplasmRegulatory Genes Found in HIV That Are

8、 Not Required for ReplicationGenesProteinFunction of ProteinnefNefDecreases CD4 proteins and class I MHC proteins on surface of infected cellsImportant for pathogenesis by SIV vifVifStabilizes newly synthesized viral DNA and transports core through cytoplasmvprVprTransports viral core from cytoplasm

9、 into nucleus in nondividing cellsvpuVpuEnhances virion release from cellHIV的受體CD4分子（靈長類動物的慢病毒屬）及輔助受體 CD4分子主要表達(dá)在淋巴細(xì)胞、單核巨噬細(xì)胞等細(xì)胞表面gp120與CD4結(jié)合，隨后與輔助受體結(jié)合，導(dǎo)致包膜構(gòu)象改變激活gp41，觸發(fā)膜融合反轉(zhuǎn)錄酶的高度錯(cuò)配性造成HIV基因組頻繁變異HIV infectin: Receptor and ligand Ligand: membrane glycoprotein: gp120This is the problem!ReplicationVirus r

10、eplication+ssRNA+ssRNA:-ssDNAssDNA:+ssDNA+ssRNAClinical findings of HIV infectionEarly phase symptoms: Flu-like symptomsLate phase manifestation: Opportunistic infections because of comprised immunityMalignant tumorsPathogenesis of HIVTarget cell and virus receptor: cells with CD4 molecules like T c

11、ells, Monocytes, macrophages, epithelium cells and some cells in CNSApoptosis of infected cells (unknown mechanisms)Clinical findings of HIV infectionEarly phase symptoms: Flu-like symptomsLate phase manifestation: Opportunistic infections because of comprised immunityMalignant tumorsLaboratory diag

12、nosis of HIV infectionMarker of infection: Anti-HIV antibodyMethod of antibody detection: ELISA technology for screening and Western blot for confirmationWHO recommended a double check with ELISA to replace Western blot testPCR method for the virus detectionTransmission of HIVSource of the virus: Bl

13、ood, semen, vaginal secretion and other body fluidMajor ways of transmission: Blood-born transmission, unprotected sex intercourse.Mother to newborn baby infectionNo evidence to prove the transmission of HIV through social contact and enteric pathwayClinical management of HIV infectionControl and tr

14、eatment of infectionAnti-virus chemotherapy with three kinds of medicine: 1. Nucleoside 2. Non-nucleoside 3. Protease inhibitor治療：雞尾酒療法（HAART）聯(lián)合交替使用2種HIV逆轉(zhuǎn)酶抑制劑和一種蛋白抑制劑（Saquinavir、Ritonavir）可有效將血液中HIV含量降到最低，極大延長感染者壽命無法清除整合的病毒，不能徹底清除病毒藥物有副作用在中國年均費(fèi)用8萬 RMBHighlyActiveAnti-Retroviral TherapyHAART: Two nu

15、cleoside analog RT inhibitors and 1 protease inhibitorNow also: Two nucleoside analog RT inhibitors and 1 non nucleosideHAART indication（2000）1. HIV1 Viral load 10-30000/ml2. CD4 value 250 cells/ml.3. Full Blown AIDS .Development of resistance我國疫情Control and prevention of HIV infectionPublic and per

16、sonal hygieneStrategy of blood precaution and eye protection.Post-exposure prophylaxis(PEP) of HIV infectionTransmission of HIVSource of the virus: Blood, semen, vaginal secretion and other body fluidMajor ways of transmission: Blood-born transmission, unprotected sex intercourse.Mother to newborn b

17、aby infectionNo evidence to prove the transmission of HIV through social contact and enteric pathwayRisk assessment of HIV infection Sexual intercourse: 5-15/10000Homo-sexual intercourse: 10-15%Mother-infant transmission: 20-60%Trauma like needle puncture): 1-3%Blood transfusion: 70-80%Sharing needles: 10-30%Challenges to the development of HIV vaccineChange of antigen epitope in gp 160 molecule, the ligand to CD4 receptor of host cellsDifficulty of stimulating cell-mediated immunity especially CD8 T cell responseSt