null Retrovirus
Retrovirus
p. 394null
I. Basic Properties:
1. +ss RNA, but double strands, three structure genes
2. Reverse transcriptase (RT)
3. Spherical, 100 nm or so
4. Replication:
RNA+ cDNA(RNA:DNA hybrid) ds DNA
host DNA
transcription
RNA mRNA
protein
assemble mature virus RTRNase HDDDPinsertionProvirusnullnullnucleuscytoplasmabuddingRetrovirus replicationnull
II. Classification:
Seven genera totally, but pathogenic to
human are only
1. Deltaretrovirus:
causing leukemia, such as
Human T cell Lymphotropic Virus---
HTLV- I, II, V types
2. Lentivirinae:
Human Immunodeficiency Virus (HIV)
null
I. Introduction:
1981. 6: 1st report in USA---Pneumocystis Carimi
pneumonia (PCP),
reported by Gottlieb, USA.
1981.7: Kaposi Sarcoma.
1982: Acquired Immune Deficiency Syndrome,
definition of AIDS;HIV1st AIDS report in the world1st AIDS report in the worldMMWRMORBIDITY AND MORTALITY WEEKLY REPORTJune 5, 1981 / Vol. 30 / No. 21Pneumocystie Pneumonia –Los AngelesIn the period October 1980-May 1981, 5 young men, all active healthy treated for biopsy-confirmed Pneumocystis carinil Pneumonia at 3 different hospitals in Los Angeles, California. Two of the patient died. All 5 patients… …null
1983: Montagnier, (French)---LAV
1984: Gallo, (U.S.A)---HTLV-Ⅲ
1986: Human Immunodeficiency Virus, (HIV).
HIV-1=HTLV-Ⅲ, LAV; (1984), world wide
HIV-2 (1986), West Africa
{null法国科学家弗朗索瓦丝-巴尔-西诺西
(Françoise Barré-Sinoussi) 法国科学家吕克-蒙塔尼
(Luc Montagnier)2008年诺贝尔医学奖得主nullLipid bilayerRNAHost componentsStructure of HIVintegrasenullproteinaseLipid bilayerRTStructure of HIVnullCross-section of HIV nullHIV genome and virion structurenull
II. Epidemiology: 15000/day=1/6sec
1. Distribution:
1). AIDS Patients: 1981—2001.10
163 Countries reports: died 22 million.
2). HIV Carriers: 36million
Africa: 25million
U.S.A: 0.90million
3). CHINA: 1985—2003.10
AIDS Patients: 84208; 1141 died
AIDS Carriers: 1 million. null2. Transmission:
1). infectious Sources:
AIDS Patients; HIV Carriers;
2). infectious routes:
(1) Sexual transmission
(2) Infectious blood: Blood products, Syringes
(drug abusers), Transplantation, etc.
(3) Mother-baby born
3. General properties
locality, young people (male>Female), homosexalnull
III. HIV biological properties:
1. Genome: +ss RNA, 9 genes, 9.2-9.8kb
Structure genes:
po1:——enzymes(P66/P51, proteinase)
gag:——Capsid(P24, P17, P7)
env:——envelope (gP41, gP120, gp160)
Regulatory genes: vif, vpu, vpr, tat, rev, nef;
2. Replication.
Reverse transcription
nullHIV-1/2 gene structure
Genome organization nullgenomeproteinsGenome and proteins of HIVnullReplicative cycle of HIVnullnull3. Variation
relative higher, especially in gP120 gene
subtypes of HIV-1: M,O,N 3 groups
M:11 subtypes
4. Resistance
weak
56oC for 10 minutes
room temperature for 7 daysnull
IV. Pathogenesis (Clinical symptoms):
long incubation; 100% died;
HIV
CD4 receptor ↓CCR5(MФ), CXCR4(T)
CD4+T ; Mononucleus cell, Mφ; Neural cells
↓
Cell death
CD4+T <200/mm3
↓
Cellular Immunity↓
HIV transmission to central Nervous system,
other monocyte, Mφ, NK…… nullnull
Mechanisms of CD4+T :
1. direct kill by CTL
2. cells fusion
3. toxicity mediated by un-integrated DNA
4. apoptosis
5. cell damage by HIV release
6. cross-reaction by auto-antibbody
null
Symptoms:
1. Primary acute infection:
2. Asymptom incubation:
3. ARC:
fever, weight↓, fatigue, diarrhea,
lymphnode enlarged;
4. AIDS:
*Opportunistic infection: Fungi, Bacteria, virus
*Tumours: Kaposi’s sarcoma
*Nerves symptoms: dementianull
V. Diagnosis:
1. Anti-HIV (primary test and confirming test)
IF+ELISA; Western blot+RIA.
2. Antigens, such as P24, RT
3. Isolation of HIV from blood.
4. HIV RNA : PCR, indicator---viral load
5. CD4+TRelationship of CD4+ and virus load-1Relationship of CD4+ and virus load-1(Lg )y=-0.0026x+4.9091
r=-0.6888 p<0.05Relationship of CD4+ and virus load-2Relationship of CD4+ and virus load-2nullCD4+ PBL4~6 weeksUp to 12 years2~3yearsplasmainfectionseroconversiondeathAnti-EnvAnti-P24HIV-specific CTLRNA copies in plasmaAsymptoms symptomsInfection dosenullVI. treatment and Control:
1. Treatmnet:
Medicine: AZT. DDI.
Vaccine: GP160.
Gene therapy:
2. Control:
health education
blood; blood products; drug abuser
sexual knowledge
mother-baby born
nullFirst NRTI appeared in in 1986
AZT
3TC,d4T,…
First NNRTI appeared in 1994
Nevirapine
First Protease Inhibitors(PIs) appeared in 1995
SaquinavirResearch on anti-HIV drugsNucleoside Reverse Transcriptase Inhibitors, NRTINucleoside Reverse Transcriptase Inhibitors, NRTIAbacavir (Ziagen, ABC)
Dedanosine (ddI, Videx)
Lamivudine (3TC, Epivir)
Stavudine (d4T, Zerit)
Zalcitabine (ddC, Hivid)
Zidovudine (ZDV; AZT, retrovir, azidothymidine)
AZT and 3TC, Combivir
ZDV+AZT+3TC,Trizivir Non-Nucleoside Reverse Transcriptase Inhibitors, NNRTINon-Nucleoside Reverse Transcriptase Inhibitors, NNRTIDelavirdine (Rescriptor)
Efavirenz (Sustiva, STOCRIN)
Nevirapine (Viramune) Protease Inhibitors, PIsProtease Inhibitors, PIsAmprenavir (Agenerase)
Indinavir (Crixivan)
Nelfinavir (Viracept)
Retonavir (Norvir)
Saquinavir (Invirase O-hard, Fortavase-soft)
Lopinavir/ritonavir (Kaletra)
Highly Active Anti-Retroviral Therapy (HAART)Highly Active Anti-Retroviral Therapy (HAART)NRTI PI/NNRTI
AZT+3TC Indinavir
AZT+DDI Lopinavir/Ritonavir
d4T+3TC Nelfinavir
d4T+ddI Ritonavir+Indinavir
Efavirenz
NNRTI PI
Efavirenz IndinavirAlternative drugs for HAARTAlternative drugs for HAARTAZT+3TC+abc
ddI+3TC /
AZT+ddCAmprenavir
Ritonavir
Saquinavir(soft)
Ritonavir+Saquinavir
Delavirdine
Nevirapine+nullREVIEWWhat are the laboratory examinations for HIV infection
and AIDS, and how to do it?
2. Do you know the transmission ways for HIV, and which
is the major way?
3. Please offer a brief proposal for human and government
concerning that how to prevent HIV transmission or
epidemic among the persons?
Pneumocystis carinii pneumoniaPneumocystis carinii pneumoniaPneumocystis: GMS stainPneumocystis: GMS stainToxo acute myocarditisToxo acute myocarditisCandida stomatitis(thrush)Candida stomatitis(thrush)Candida esophagitisCandida esophagitisCryptococcosisCryptococcosisCRYPTOSPORIDIOSISCRYPTOSPORIDIOSISHERPESHERPESHERPESHERPESHerpes inclusions (pneumonia)Herpes inclusions (pneumonia)Kaposi’s sarcoma in AIDSKaposi’s sarcoma in AIDSnullKaposi’s sarcoma in AIDSnullnull千学万学学做真人有知识更要有文化有智慧更要有责任