HIV and AIDS

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HIV and AIDS

• Retrovirus -gt
• Primate Lentivirus Group

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Retrovirus

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

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HIV-1
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HIV Structure Generalized
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HIV Structure ID
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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

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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

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HIV core

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

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Capsid, p 24
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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

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HIV Structure Summary
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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

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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

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Integrase Enzyme
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Other Proteins

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

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Protease Enzyme
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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

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HIV Life Cycle
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Attachment

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

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Penetration and Uncoating

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

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Genome Replication

• V-tRNA as primer
• RT ? ss RNA ? ss-DNA ? ds DNA
• Proviral DNA
• Linear
• circular
• Integrase
• Incorporates vDNA into host cell genome

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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

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Assembly and Budding

• Capsid assembly at plasma membrane
• Host plasma membrane for viral envelope
• Viral proteins become spikes on envelope

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HIV Life Cycle Summary
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Viral Replication
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HIV infected T lymphocytes
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HIV Cycle Animation
http//www.galaxygoo.org/hiv/hiv_l
ifecycle.html
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Transmission

• Horizontal
• Blood 90
• Organ, transfusion
• Coitus
• Vertical
• Direct
• Infected cell
• Body fluids

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Signs and Symptoms

• Prodromal
• Early Phase
• Flu-like
• Middle Phase
• Asymptomatic
• Destruction / Loss gt than replacement
• Late Phase
• AIDS

• Stages of HIV
• Category A
• lymphadenopathy
• Category B
• Opportunistic infections
• Category C
• AIDS
• Persistant opportunistic infections

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Diagnosis

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

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Opportunistic Infections
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Treatment
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HIV Animation for Drug Tx
http//www.hopkins-aids.edu/hiv_lifecycle/hivcycle
_txt.html
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HIV Poster of Life Cycle