1. HIV and AIDS Retrovirus -> Primate Lentivirus Group

2. Retrovirus Linear, 2 ss +RNA tRNA lys Reverse Transcriptase Helical core Icosahedral capsid Phospholipid Envelope Spikes

4. HIV-1

5. HIV Structure Generalized

6. HIV Structure: ID

7. HIV Envelope Derived from host cell plasma membrane Viral proteins as spikes Cap, gp 120 Binds to CD4 Linked to TM stem Can change shape Stem, gp 41 Holds cap in envelope Responsible for membrane fusion

9. Matrix, p17 Continuous inside membrane lining for envelope Icosahedral Functions Anchors TM, p41 Assist in viral penetration Transport proviral integration complex across nuclear envelope Localizes virion assembly

10. HIV core RNA genome Nucleocapsid Reverse Transcriptase (RT) Integrase (IN) HIV core appears conical / helical

11. Capsid, p 24

12. Nucleocapsid NC p 6, 9 helical RNA 2 ss + Multiple genes RT vRNA  vDNA tRNA lys 3 Primer for RT Integrase, p 32 Integration of vDNA into host DNA

13. HIV Structure Summary

14. RNA genes for HIV All retroviruses have 5’ – gag – pol – env – 3’ HIV have 3 genes for replication: gag, pol, env 3 genes for regulation: tat, rev, nef 3 genes for auxiliary: vir, vpr, vpu

15. HIV RNA Gag genes Capsid protein, p 24 Matrix protein, p 17 Nucleocapsid, p6, p9 Pol genes Protease, p 11, p9 RT, p55, p63 Integrase, p 32 Env genes Surface glycoprotein, gp120 Transmembrane protein, gp 41

16. Integrase Enzyme

17. Other Proteins Vpu Viral protein U Enhances viral particle release Vpr Viral protein R Changes ion channel activity, vRNA -> nucleus Protease Hydrolytic enzyme used for viral replication Cleaves large viral proteins into functional peptides

18. Protease Enzyme

19. More Proteins Nef : negative factor Signal transduction Binds to cellular protein kinases Endocytosis of surface receptors Down grades CD4 protiens Destruction Apoptosis of non-infected cells

20. HIV Life Cycle

21. Attachment SU envelope protein [gp 120] Binds to CD4 Infects macrophages Co-receptor chemokine CCR5 on macrophages CXCR4 on T-helper

23. Penetration and Uncoating TM, gp 41 Conformational change after SU, gp 120 binds and co-receptor stimulated Partial uncoating In cytoplasm

25. Genome Replication V-tRNA as primer RT  ss+ RNA  ss- DNA  ds DNA Proviral DNA Linear circular Integrase Incorporates vDNA into host cell genome

26. Translation Proviral DNA Create mRNA Create new ss+ RNA Fresh vRNA enters cytoplasm Latent Mutations Protease Cleaving of viral proteins in order to have functional protein products

27. Assembly and Budding Capsid assembly at plasma membrane Host plasma membrane for viral envelope Viral proteins become spikes on envelope

28. HIV Life Cycle Summary

29. Viral Replication

30. HIV infected T lymphocytes

31. HIV Cycle Animation http://www.galaxygoo.org/hiv/hiv_lifecycle.html

32. Transmission Horizontal Blood – 90% Organ, transfusion Coitus Vertical Direct Infected cell Body fluids

33. Signs and Symptoms Prodromal Early Phase Flu-like Middle Phase Asymptomatic Destruction / Loss > than replacement Late Phase AIDS Stages of HIV Category A lymphadenopathy Category B Opportunistic infections Category C AIDS Persistant opportunistic infections

34. Diagnosis IgG Infection Seroconversion Verify with Western Blot ELISA p24 capsid antigen PCR vRNA

35. Opportunistic Infections PCP Pneumocystis carnii Cytomegalovirus Mycobacterium Fungal: Candidia Systemic Protozoan: T. Gondii Isospora Viral: Herpes HSV-1, VZV, EBV Neoplasms: Kaposi’s sarcoma Lymphoma Misc: Lymphoid pneumonitis Dz: Pneumonia, GI, brain, LN, blindness

36. Treatment SupportiveNucleoside analogs that interfere with RT Nonnucleoside inhibitors of RT Protease inhibitors blocks cleaving of proteins Entry inhibitors that interfere with fusion protein HAART: Highly Active AntiRetroviral Therapy

37. HIV Animation for Drug Tx http://www.hopkins-aids.edu/hiv_lifecycle/hivcycle_txt.html

38. HIV Poster of Life Cycle