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1、Chapter 25,Retrovirus,逆转录病毒,Pathogenic retrovirus to human,1.Human T-cell lymphotropic virus (HTLV) 2.Human immunodeficiency virus (HIV),Characteristics of retrovirus,p323,Introduction,-球形、+ssRNA二聚体、有包膜病毒，含逆转录酶,Human Immuno- deficiency Virus,人类免疫缺陷病毒,Pathogen of AIDS,1.Shape and tructure,脂双层膜,gp41,p
2、24衣壳蛋白,p14内膜蛋白,p7核衣壳蛋白,逆转录酶,蛋白酶, Nucleocapsid,(icosahedral),(d=80120nm), Core (圆柱形) +ssRNA and enzymes structural protein,RNA, Envelope, lipid bilayer gp120 and gp41,lipid bilayer,gp120,gp41,p24,p7,p17,RT,proteinase,integrase,.Biological properties,* p7 (核衣壳蛋白) * p24 (衣壳蛋白) * p17 (内膜蛋白),2.Genome of
3、HIV,Consists of 2 identical +ssRNA (dimer),Contain 3 structural genes (gas, pol, env) and 6 regulatory genes,p7,p17 and p24,RT,gp120 and gp41,特异性最高，p24+常 作为病毒感染的标志,有与CD4分子结合部位,(有些序列高度易变),介导病毒包膜 与细胞膜融合,其中的nef基因编码的Nef蛋白是HIV感染后发展为AIDS的重要因子,3.Viral variation, Variation of env gene, Variation of nef gene
4、,variation of gp120 (V3 region) change of cell tropism,-encode negative regulatory proteins expression of viral proteins ,5.Resistance,(weak),4. Cultivation,(CD4+ cells),1.Source of infection and route of transmission, Source of infection, Route of transmission,by sexual contact (性接触) hematogenic tr
5、ansmission (血源性传播) vertical transmission (垂直传播),patients with AIDS asymptomatic HIV carriers,(anti-HIV+者),.Pathogenicity and Immunity,2. cell tropism & viral receptor, Cell tropism of HIV, Tropism to CD4+cells T-tropic strain and M- tropic strain,*T-tropic strain-CXCR4 *M-tropic strain -CCR5,gp120 b
6、inds to v1 region of CD4 molecule, Viral receptor, Specific receptor- CD4 molecule co-receptor-chemokine receptor,(嗜T细胞病毒株) (嗜M 病毒株),(gp120 V3 region binding to co-receptor), acute infection period latent period immunologic deficiency period,ofter asymptomatic,self limiting and non-specific symptom,
7、病毒,(210年),AIDS-related complex (ARC,艾滋病相关症候群),activate,AIDS,3. HIV-infection,(CD4+ T cell ),Only infect CD4+cell Cause “slow” infection with long incubation periods Resulting in severe immuno- deficiency-acquired immuno- deficiency syndrome (AIDS),Feature,获得性免疫缺陷综合征(艾滋病), ARC various opportunistic i
8、nfections certain cancer CNS symptoms,(Kaposi 肉瘤和恶性淋巴瘤),(AIDS痴呆综合征),4.Immunity,Neutralizing antibodies Cellular immunity,(ADCC, CTL, NK cell,etc.),-anti-gp120 (except anti-p24),免疫力不足于彻底清除病毒,一经感染便终身携带病毒,.Laboratory Diagnosis,1.Detection of antibody 2.Detection of virus and viral components, p24 antig
9、en viral RNA isolation of virus,ELISA ; IFA; RIA and WB (免疫印迹) anti-p24 and anti-gp120,同时检出二种抗体即可诊断,p24+常作为病毒感染的标志,.Prevention & Therapy,1.General prevention (p327) 2.Vaccination 3.Antiviral therapy,(AZT ; ddI/ddC/ddT and 3TC,etc.),叠氮胸苷；双脱氧肌苷/双脱氧胞苷/双脱氧胸肌苷和拉米夫定,Pathogen of ATL,Human T-cell Lymphotrop
10、ic Virus,人类嗜T细胞病毒,(成人T细胞白血病),2. Pathogenicity, Source of infection, Route of transmission, hematogenic transmission sexual contact vertical transmission, Pathogenesis,(only infect CD4+ T cells and cause T-cell leukemia),无症状携带者和患者,1.Shape and tructure,similar to HIV ( p17 p18), HTLV-1,cause adult T-cell leukemia (ATL) the cause of tropical spastic paraparesis (TSP) and B-cell lymphoma, HTLV-2,causes hairy-cell leukemia chronic CD4+ cell lymphoma,Mechanism of HTLV causing leukemia,热带下肢痉挛性瘫痪,毛细胞白血病,tax和rex 的基因产物反式激活CD4+ T细胞的IL2基因和IL2R 基因 异常表达细胞大量增殖并转化 为白血病细胞,
