浙江大学：Human Immunodeficiency Virus and Acquired Immunodeficiency Syndromes

Human Immunodeficiency Virus and Acquired Immunodeficiency Syndromes Dongli pan Department of Medical Microbiology and Parasitology Zhejiang University School of Medicine pandongli@zju. edu.cl

Human Immunodeficiency Virus and Acquired Immunodeficiency Syndromes Dongli Pan Department of Medical Microbiology and Parasitology Zhejiang University School of Medicine pandongli@zju.edu.cn

DNA Viruses RNA Viruses Group I Group‖l Group Ill Group Group V Group VI Group VI DNA(+/-) DNA (+ RNA(+/-) RNA(+) RNA(-) RNA(+) DNA(+/-) ranscription DCOOOOOO RNA(-) DNA(+/- Reverse transcription RNA prot Baltimore classification Fields Virology 6th edition

Fields Virology, 6th edition DNA viruses RNA viruses Baltimore classification

People estimated to be living with HIV(2014 WORLD AIDS DAY Eastern Euro North America and Western and Central Europe&Central Asia 2.4 million [1.5 million- 3.5 milionI (1.3 million-1.8 million) Middle East North Africa bean 240000 000 1500032000 Asia and the Pacific n2100004000 5.0 million Sub- Saharan Africa 种5 millIon=56moh Latin America 25.8 millior 1.7 million 240 [4 million-2.0 million Total: 36.9 million [34.3 million.4 million

People estimated to be living with HIV (2014)

How was hi discovered 1980-1981, 5 young men, all active homosexuals, were treated for Pneumocystis carini pneumonia(PCP)in LA, CA. The symptoms suggest the possibility of cellular-immune dysfunction Clusters of PCP and Kaposi's sarcoma observed in other hospitals 1982 disease started to be called aids Found transmitted at birth and heterosexually Virus was first isolated in 1983 from the lymph node of a patient with lymphadenopathy in Paris 1984 Electron microscopy and sequence anal ysis revealed hiv to be a lentivirus, known group of retroviruses

How was HIV discovered • In 1980-1981, 5 young men, all active homosexuals, were treated for Pneumocystis carinii pneumonia (PCP) in LA, CA. The symptoms suggest the possibility of cellular-immune dysfunction. • Clusters of PCP and Kaposi’s sarcoma observed in other hospitals. • 1982 disease started to be called AIDS. • Found transmitted at birth and heterosexually. • Virus was first isolated in 1983 from the lymph node of a patient with lymphadenopathy in Paris. • 1984 Electron microscopy and sequence analysis revealed HIV to be a lentivirus, known group of retroviruses

Where is hiv from Hr-2 Vsmr Syes's monkey Sooty SiVgsnSiVmus/SIMon SIVsyk) s/vamn Ptt of central africa StOol SiMon Mantled guereza Mona monkey HIV-1 M&N SIvcpz SIVe SIRcam chimpanzee s/Vho(s/vmnd SIVcpz SIVer Vervet monkey Red-capped HiV-1 P60 /estern goia LHoest's monkey Mandrill Cold Spring Harb Perspect Med 2011: 1:0006841

Where is HIV from

Structure of HIv particle ·Core +ssRNA copies P orease Docking Glycoprotein reverse transcriptase (RT, an rna dependent dna Lipid RNA gp41 Membrane polymerase Transmembrane Glycoprotein 1 capsid (P24) P24 gaopI Matrix protein · Envelope Integrase gp120 Nucleocapsid Reverse Transcriptase o vif, Vpr, Nef and p7 Diameter: N 100 nm www.wikidoc.org

• Core – +ssRNA 2copies – reverse transcriptase (RT, an RNA dependent DNA polymerase) – P24 • Envelope --gp120 --gp41 Diameter: ~ 100 nm (P24) Structure of HIV particle www.wikidoc.org

HIV genome LTR LTR tat. gag vif vpr vpu tat nef rev 1 RNA 10 kb),9 genes long terminal repeat,LTR(5’,3’-end) 长末段重复序列 ·3 structura| genes gag >P55>P24, P17, P6, P7 pol >RT, integrase rNase h and protease env> glycoprotein(gp120 and gp41 6 regulator genes tat, rev and nef are most important

HIV genome • 1 RNA (~ 10 kb), 9 genes • long terminal repeat, LTR (5’, 3’- end) • 3 structural genes – gag → P55 → P24, P17, P6, P7 – pol → RT, integrase, RNase H and protease – env → glycoprotein (gp120 and gp41) • 6 regulator genes tat, rev and nef are most important 长末段重复序列

Replication cycle of HIv GP120 reverse transcriptase capside Integrase protease RNA Attachment HIV CD4 Endocytosis CCR5 or CXCR4 co-receptor clathria Limited proteolysis Assembl and release Translation (protein synthesis) Removal of the protein envelopes mRNA o Revers transcriptation Integrationg Transcription ● cellular dna Watch video http://www.hhmi.org/biointeractive/hiv-life-cycle

Replication cycle of HIV http://www.hhmi.org/biointeractive/hiv-life-cycle Watch video:

HIV entry: one receptor two co-receptors Receptor: CD4 CD4 Coreceptor Virus-Cell Binding Binding Fusion Coreceptor: CCR5/CXCR4 HIV gp41 HIV targets cD4* cells the gp120 -V3 loop major targets are CD4* t cells D4 But it can also infect Host monocytes, macrophages cell CCR5/CXCR4 dendritic cells, etc. HIV (X4) HIV(R5) c-chemokine chemokine -chemokine (CCI 3, CCI 4) CD4* target cell arget cell

Receptor: CD4 Coreceptor: CCR5/CXCR4 HIV entry: one receptor, two co-receptors HIV targets CD4+ cells. The major targets are CD4+ T cells. But it can also infect monocytes, macrophages, dendritic cells, etc

HIV types and subtypes HIV's genome is highly variable Reverse transcriptase of Hiv does not have proofreading activity HIV has two types: HIV-1 and HIv-2 HIV-1 is more common more virulent and more infectious than hiv-2 Each type has many subtypes R Global Total 32%53% 53% 26.7% 472%(2.3% 口 Subtype A口 Subtype B口 Subtype C 口 Subtype D口 CRF AE■ Others www.wikidoc.org

HIV types and subtypes www.wikidoc.org • HIV’s genome is highly variable • Reverse transcriptase of HIV does not have proofreading activity • HIV has two types: HIV-1 and HIV-2 • HIV-1 is more common, more virulent and more infectious than HIV-2 • Each type has many subtypes