医学微生物学资料：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模型图脂双层膜gp120gp41包膜糖蛋白p24衣壳蛋白p17内膜蛋白p7核衣壳蛋白逆转录酶蛋白酶整合酶基因组全长9.2KB两端含长末端重复序列（LTR）3个结构基因（env、pol、gag）6个调节基因（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的受体CD4分子（灵长类动物的慢病毒属）及辅助受体 CD4分子主要表达在淋巴细胞、单核巨噬细胞等细胞表面gp120与CD4结合，随后与辅助受体结合，导致包膜构象改变激活gp41，触发膜融合反转录酶的高度错配性造成HIV基因组频繁变异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治疗：鸡尾酒疗法（HAART）联合交替使用2种HIV逆转酶抑制剂和一种蛋白抑制剂（Saquinavir、Ritonavir）可有效将血液中HIV含量降到最低，极大延长感染者寿命无法清除整合的病毒，不能彻底清除病毒药物有副作用在中国年均费用8万 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我国疫情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