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HIV and AIDS

This overview delves into the intricate structure and life cycle of the HIV retrovirus. HIV, a member of the Primate Lentivirus group, is characterized by its linear, 2-stranded RNA, reverse transcriptase, and lipid envelope with protein spikes that facilitate CD4 binding. We explore key components such as the gag, pol, and env genes, the role of viral proteins in replication and infection, and the stages of HIV infection from attachment to asymptomatic and AIDS stages. Understanding these mechanisms is crucial for developing effective treatments and interventions against HIV/AIDS.

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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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