HIV and AIDS

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. 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 Signs and Symptoms

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

35. Opportunistic Infections

36. Treatment

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

38. HIV Poster of Life Cycle