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HIV and AIDS

HIV and AIDS. Retrovirus -> Primate Lentivirus Group. Retrovirus. Linear, 2 ss +RNA tRNA lys Reverse Transcriptase Helical core Icosahedral capsid Phospholipid Envelope Spikes. HIV-1. HIV Structure Generalized. HIV Structure: ID. HIV Envelope. Derived from host cell plasma membrane

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HIV and AIDS

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  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

  3. HIV-1

  4. HIV Structure Generalized

  5. HIV Structure: ID

  6. 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

  7. 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

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

  9. Capsid, p 24

  10. 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

  11. HIV Structure Summary

  12. 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

  13. 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

  14. Integrase Enzyme

  15. 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

  16. Protease Enzyme

  17. 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

  18. HIV Life Cycle

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

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

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

  22. 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

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

  24. HIV Life Cycle Summary

  25. Viral Replication

  26. HIV infected T lymphocytes

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

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

  29. 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

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

  31. Opportunistic Infections

  32. Treatment

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

  34. HIV Poster of Life Cycle

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