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34 - Retrovirus R e tr o v ir id a e R N A t u m o r v ir u...

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Unformatted text preview: Retrovirus R e tr o v ir id a e R N A t u m o r v ir u s g r o u p O n v ir in a e RNA 含含含含含含 R o u s s a r c o m a v ir u s M u r in e s a r c o m a v ir u s M o u s e m a m m a r y t u m o r v ir u s M a e d i/ V is n a g r o u p L e n t i v i r in a e 含含含含含 H IV I, H IV II S h e e p v is n a v ir u s E q u i n e i n f e c t i o u s a n e m i a v ir u s F o a m y v ir u s g r o u p S p u m a v ir in a e 含含含含含含 含含含含含含 H u m a n f o a m y v ir u s Retrovirus Retrovirus 含含含含含含 RNA 含含 含含含含含含含含 含含含含含含含含 含含含 100­140nm 含含含含含含含含含含含 含含含含含含含含含 +ssRNA 含含 5‘ 含含含含含含含含含含含含 9­ 10 KB 含含含含含含含含含含含含含含含含含含含含含含含含含含含 C 含含 D 含含含含含 含含含含含含含含含含含含含含含含 gag 含 pol 含 env 含含含含含含含 含含含含含含 含含含含含含含含含含含含含含含 RNA 含 H 含含含含 : 含含含含含含含含含含含 cDNA 含含含含含含含含含含含含 含 Provirus 含 含含含含含含含含含含含含含含含 含含含含含含含 含含含含含含含 Human Immunodeficiency Human Virus, HIV Virus, 含含含含 含含含含 1981 年 6 年年年 CDC 年年年年年 5 年年 Los Angeles 年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年 年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年 CNS 年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年 Aquired Immunodeficiency Syndrome, AIDS 年 1983 年年 1984 年年 AIDS 年年年年年年年年年年年年年年年年年年年 Lymphadenopathy­ associated virus 年 LAV 年年年年年 T 年年年年年年 III 年年 Human T­ lymphotrophic virus type III 年 HTLV­III 年年 AIDS 年年年年年 AIDS­related retrovirus 年 ARV 年年年年年年年年年年年年年年 1986 年年年年年年年年年年年年年年 Human immunodeficiency virus, HIV 年 含含含 type 含 含含含 含含含含含含含含含 AIDS 含含含含含含含含含含含含含含含含含 70% 含含含含含含含含 HIV 含含含 HIV­1 含含含含含含含含 HIV­2 含含含含含含含 含含含 HIV 含含含 HIV­1 Viral genome Viral 9.2kb +ssRNA with three structual genes 9.2kb and six regulatory genes. and 含含含含含 9.2KB 含含含含含含含含含含含 LTR 含 3 含含含含含含 env 含 pol 含 gag 含 6 含含含含含含 tat 含 rev 含 nef 含 vif 含 vpr 含 vpu 含 含含含含含 Strucutre Genes 含 含含含含含 Gene gag Encoded Protein Function of Protein Matrix Reverse transcriptase Protease Transcribes RNA genome into DNA Integrase env Nucleocapsid p17 pol P24, p7 Integrates viral DNA into host cell DNA gp120 Attachment to CD40 protein Cleaves precusor polypeptides 含含含含含 Regulatory Genes 含 含含含含含 vif viral infectivity factor tat transactivating protein vpu viral protein U rev regulator of virion protein expression nef negative regulatory factor Regulatory Genes Found in HIV That Are Required for Replication That Gene Protein Protein Function tat Tat Activation of transcription of viral genes rev Rev Transport of late mRNA from nucleus to cytoplasm Regulatory Genes Found in HIV That Are Not Required for Replication Are Genes Protein nef Nef Function of Protein Decreases CD4 proteins and class I MHC proteins on surface of infected cells Important for pathogenesis by SIV Stabilizes newly synthesized viral DNA and transports core through cytoplasm vif Vif vpr Vpr Transports viral core from cytoplasm into nucleus in nondividing cells vpu Vpu Enhances virion release from cell Replication Replication Viral dynamics in a typical HIV+ person[1] •Error frequency in RT: 3 x 10 ­ 5 per base per replicat ion cycle •HI V­ 1 genom e is com posed of 10 4 = 10,000 nucleot ides •up t o 10 billion viruses are produced daily •100 m illion new cell infect ions/ day •10 m illion viruses per day w it h one new "error" ( m ut at ion) HIV env genetic subtypes (1998) env Adapted from J. Mullins 年年年年 年年年年 HIV 含含含含含含含含含含含含含含含含 CD4 含含含含含含含含含含含含 PHA 含含 3 含含含含含含 T 含含含含含含含含含含含含含含含含含含含含含含含 CPE 含含含含含含含含含含含含含含含含含含含含含含含含含含含 含含含含含含含含含含 含含含含含含含含含含含含含含含含含含含 AIDS 含含 含含含含含含 含含含含含含 含含含含含 • 含含含含含含 7 含 • 含含含 56°C30min 含含含含含含含含含含含含 0.5% 含含含含含 10% 含含含含 50% 含 含含 35% 含含含含 0.3%H2O2 含 5% 含含含 10min 含含含含含含 • 含含含含含含 68 °C72h 含含含含含含含含含含含 WHO 含含含 100°C 20min 含含含含含含含 20min 20min 年年年年年年年年 年年年年年年年年 含含含 HIV 含含含含 AIDS 含含 含含含含含含含含含含含含含含含含含含含含含含含 含含含含 含含含含 含含含含含含含含含含含含含含含含 含含含 HIV 含含含含 22% 含含含含 含含 72.4% 含 AIDS 含含含含含含含含 HIV 含含含 含含含含 含含含含 4 含含含含含含含含含含 10 含含含 含含含含 含含含含 含含含含 含含含含含 含含 AIDS 含含 年年年年 • HIV 含含含含含含含 8­12 含含含含含含含含 3­6 含含含含含含含含 50­70% 含含含含含含含含含含 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 年年年年 含含 6 含 ­10 含含含含含含含 含含 AIDS 含含含含含含含 AIDS­related complex, ARC 含 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含含 AIDS 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 Kaposi 含含含 含含含 Protozoal 含 含含含含含含含含 pneumocystis carinii 含 now thought to be a fungi 含含 toxoplasmosis, crytosporidosis 含含含 Fungal 含 含含含含含含含含 candidiasis 含含含含含含含含含含 crytococcosis 含 , histoplasmosis, coccidiodomycosis 含含含 Bacterial 含 含含含 Mycobacterium avium complex 含 , 含含含含含含含含含 atypical mycobacterial disease 含 , 含含含含含含含 salmonella septicaemia 含 , 含含含含 含含含含含含含含含 multiple or recurrent pyogenic bacterial infection 含 含含含 Viral 含 CMV, HSV, VZV, JCV 含含含含含含含含含含含含含含含含含 5 含含含含含含含 90% Kaposi’s Sarcoma Sarcoma Pneumocystis Pneumocystis carinii carinii With dissemination to With dissemination to extrapulmonary sites, Pneumocystis carinii tends to produce foci with prominent calcification, as seen in the kidney here grossly With giemsa stain at high magnification, the faint bluish dot­ like intracystic bodies of Pneumocystis carinii in lung are seen in this cytologic preparation from a bronchoalveolar lavage Candida Albicans Candida Candida infections are common with AIDS, but most often appear as oral thrush, which is a nuisance but not life-threatening. Disseminated infections are uncommon, but here is a rare Candida pneumonia, which resembles a bacterial bronchopneumonia. Clincal Response Clincal Exposue to HIV No infection Persistent generalized lymphadenopathy Infection AIDSrelated complex AIDS Acute disease Asymptomic Neurological disease 年年年年 Cell tropism: CD4+ T cells, Macrophages 含 CD4+ 含含含含含 含含含含含含含含含含含含含含含含含 含含含含含含含含含含含 含含含含含含含 HIV 含 CD4+ 含含含含含 HIV 含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含含含含含含含含 cDNA 含含含含含含含含含 含含 T 含含含含含 HIV gp120 含含含含含含含含含 CD4 含含含含含含含含含含含含含含含含含含含 含含含含 T 含含含含 含含含含 含含含含 含含含含含含 HIV 含含含含含含含含含含含 CTL 含含含含含含含含含 含含含含含含 HIV 含含含含含含含含含含含含含含含含含 ADCC 含含含含 HIV 含 gp120 含 T 含含含含含 MHC II 含含含含含含含含含含含含 gp120 含 含含含含含 T 含含含含含含含含含含含含含含含含含含含 T 含含含含含含含含含含 年年年年年年年年年 年年年年年年年年年 HIV 含含含 B 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含含 含含含含含含含含含含含含含含含 CD4 含含含 HIV 含含含含含含含含含含含 HIV 含含含含含含含含 含含含含含 CPE 含含含含含含含含 HIV 含含含含含含含含含含含含含含含含含含含含含含含含含含 含含含含含含含含含 IL­2 含含 ­IFN 含含含含含含含含含 含含含含含含含 含含含含含含含 含含 40%­90% 含 AIDS 含含含含含含含含含含含含含 HIV 含含含含含含含含含含含含含含含含 含含含含含含含含含含含含含 CNS 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含 含含含含含含含含含 含含含含含含含含含 CD4+ T 含含含含含含含含含含含含含含含含 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含“含含含”含含 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含含含含含含 含含含含含含 含含含含 • 含含 ELISA RIA IFA Western blot 含含 RNA PCR 含含含含含 HIV 含含含含含含含含含含含含 HTLV 含含含含含 含含含含含含含含含含含含含含含含含含 含含含含含含 Western blot 含含 含含含含含含 ELISA for HIV antibody ELISA Screening tests should be as sensitive as possible Microplate ELISA for HIV antibody: coloured wells indicate reactivity Western blot for HIV antibody Western Confirmatory tests should be as specific as possible There are different criteria for the interpretation of HIV Western blot results e.g. CDC, WHO, American Red Cross. The most important antibodies are those against the envelope glycoproteins gp120, gp160, and gp41 p24 antibody is usually present but may be absent in the later stages of HIV infection 含含含含 : ORA HIV 含含含含 含含含含含含含含含含含含含含含含含含 HIV 含含含含含 20 含含含含含含含含含含 含含含含含含含 HIV 含含含含含含 1 含 2 含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含含含含 10 含 15 含含 含含含含含含含含含含含 FDA 含含含含 2002 含 11 含含含含含含含含含含 含 含含 含含 HIV 含含含 AIDS 含含含含含含含含含含含含含含含 含含含含含含含含含含含含含含含含含含含 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含含含含含含含含含含含含 VIII 含含含 含含含含含含含含含含 含含含含含含含含含含含含含含含含含含 年年年年年年年年年 HAART 年 年年年年年年年年年 含含含含含含 2 含 HIV 含含含含含含含含含含含含含含 含 Saquinavir 含 Ritonavir 含含含 含含含含含 HIV 含含含含含含含含含含含含含含含含 含含含含含含含含含含含含含含含含含含 含含含含含含 含含含含含含含 8 含 RMB RMB Highly Active Anti­Retroviral Therapy HAART: Two nucleoside analog RT inhibitors and 1 protease inhibitor Now also: Two nucleoside analog RT inhibitors and 1 non nucleoside HAART 含含含含含 2000 含 1. HIV1 Viral load > 10­30000/ml 2. CD4 value < 250 cells/ml. 3. Full Blown AIDS …. 100 40 80 30 60 20 40 10 20 0 0 含含含含含含含含含含 含含含含含含含含含含 含含含含 含含含含 2003 含含含含含含含 2003 含含 2002 含含含含含含含含含含含含含含含含含 40560 含含含 2001 含含含含含含 32.0% 含含含含含含含含含含含含含 2001 含含含 2000 含含含含 36.5% 含含含含含含含 含含 2 639 含 , 含 2001 含含含含 65.6% 含含含 1 047 含 含含含含含含含含含含含含含含含含含含含含 63.7% 含 25828 含含含含含含含含 8.1 含含含含含含含含含含含含含含含含含含含含 63.7% % 含 3292 含含含含含含含含含含含含 9.3 % 含 3776 含含 3776 含含含含含含含含含含 2002 含含含含含含含含含含含含含含含 100 含含 2002 含含含含含含含含 2002 2002 含含含含含含含含含含含含含含 含含含含含含含 9824 含 • 含 2001 含含含含 19.5 % 含含含含含含含含含含含含含 2001 含含 2000 含含含含 58% 含 • 含含 1045 含含含 2001 含含含 46.4% • 含含 363 含 HIV 含含含含含含含含 HIV 含含含含 20—39 含含含 含含含含含含含 含含含含含 5.2 : 1 含含含含含 5.2 : 1 含含含含含含含含含含含含含含含 63.7% 含含含含含含含含含 8.1% 含含含含 9.3% 含 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 70% 含含含含含含含含含含含 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含 含含含含含含含含含含含含含含含 含含含含含含 18 含含含含含含含含含含含含含含含含含含含含含含含含含 1998 含 2 含含含含含含含含含含含含含含含 含含含含含含 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 1350CC 含含含含含含含 304 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含含含含含含含含含含含含含含含含含含含含含含含含含含含含“含含含含含含含”含含含含含含含含含含“含含含含含”含含含含含含含 含含含含含含含含含含 15 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含含含含含含 含含含含含含含含含含含含含 年年 含含含含含含含含含含含含含含含含含 1998­2010 含含含 含含含含含含含含含含含含含含含含 2001­2005 含含含 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 年年 年年 含含含含含含含含含含含含 含含含含含含含含含含含 含含含含含含含含含含含 含含含含含含含含含 • 含含含含 22 含含含含含 11 含含含含含含含含 6000 含含含含 含含含含含含含含含含含含含含含含含含含 含含含含含含含含 含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含含含含含含含含含含含 含含含含含含含含含含含 含含含含含含含含 含含含含 含含含含含含含含含含含 含含含含含含含 1998 含 12 含 1 含 2004:“ 含含含含含含含含含”含 含含含含含含含含含”含 2003 含“ Live and let live”“ 含含含含 , 含含含含”含 含含含含”含 2002 含 • Live, Let Live • 含含含含含含含含含含含含含含含含含含含 2001 含含含含含含含含含含含含含含含 2000 含 • 含含含含含含含含含含含含含含含含 1999 Listen ,Learn, Live! 含含含含含含含含含含含 ­­ 含含含含含含含含 1998 Force for Change:World AIDS Campaign with Young People 含含含 ­­ 含含含含含含含含含 1997 Children Living in a World with AIDS 含含含含含含含含含含含含含 1988 Join the Worldwide Effort 含含含含 , 含含含含 含含含含 1989 Our Lives ,Our World ­­Let‘s Take Care of Each Other 含含含含含 , 含含含含含 ­­ 含含含含含含含 1990 Women and AIDS 含含含含含含 含含含含含含 1991 Sharing the Challenge 含含含含含含含含含含 含含含含含含含含含含 1992 A Community Commitment 含含含含含 , 含含含含含含 含含含含含含 1993 Time to Act 含含含含 , 含含含含 含含含含 1994 AIDS and the Family 含含含含含含 含含含含含含 1995 Shared Rights,Shared Responsibilities 含含含含 , 含含含含 含含含含 1996 One World,One Hope 含含含含 , 含含含含 含含含含 含含含 T 含含含含含 HTLV 含 Human T含含含 Cell Lymphotropic Virus 年年 年年 1978 含含 T 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 C 含 含含含含含含含含含含含 T 含含含含含 Human T­cell lymphotropic virus, HTLV 含含含含 T 含含含含含含含 含 Human T­cell leukemia virus, HTLV 含 含含含含含含含含含含含含含含含含含含含含含含含含 T 含含含含含含含含含 HTLV II 含含 含含含含含含 HTLV I 含含含含含含含含含 50% 含含含 含含含含含 含含含含含 含含含 100nm 含含含含含含含含含含含含含含含含含含含 gp120 含含含含含含含 p24 含 p18 含含含含含含 LRT 含含含含含含 HIV 含含 含含含 含含含 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 I 含含 II 含含含含含含 T 含含含含含含含含含 40 含含含含含含含 T 含含含含含含含 含含 II 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含含含含 含含含含 含含含含含含含含含含 RNA 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含 含含含含含含含含含含含含 IL­2 含含含含 IL­2 含含 CD4+ 含含含含含含 含含含含含 含含含含含 含含含含含含含 • 含含含含含含含含含含含含含 PHA 含含含含含 IL­2 含含 3—6 含含含含含含含含 C 含含 含含含 含含含含 (HTLV 1 specific antibody) • ELISA • 含含含含含含 ...
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