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
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
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
HIV core
RNA genome
Nucleocapsid
Reverse
Transcriptase (RT)
Integrase (IN)
HIV core appears
conical / helical
Capsid, p 24
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
HIV Structure Summary
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
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
Integrase Enzyme
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
Protease Enzyme
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
HIV Life Cycle
Attachment
SU envelope protein
[gp 120]
Binds to CD4
Infects macrophages
Co-receptor
chemokine
CCR5 on
macrophages
CXCR4 on T-helper
Penetration and Uncoating
TM, gp 41
Conformational change after SU, gp 120
binds and co-receptor stimulated
Partial uncoating
In cytoplasm
Genome Replication
V-tRNA as primer
RT ss+ RNA ss-
DNA ds DNA
Proviral DNA
Linear
circular
Integrase
Incorporates vDNA into
host cell genome
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
Assembly and Budding
Capsid assembly at
plasma membrane
Host plasma
membrane for viral
envelope
Viral proteins
become spikes on
envelope
HIV Life Cycle Summary
Viral Replication
HIV infected T lymphocytes
HIV Cycle Animation
http://www.galaxygoo.org/hiv/hiv_lifecycle.html
Transmission
Horizontal
Blood – 90%
Organ, transfusion
Coitus
Vertical
Direct
Infected cell
Body fluids
Signs and Symptoms
Prodromal Stages of HIV
Early Phase Category A
Flu-like lymphadenopathy
Middle Phase Category B
Opportunistic
Asymptomatic infections
Destruction / Loss > Category C
than replacement
AIDS
Late Phase Persistant
AIDS opportunistic
infections
Diagnosis
IgG
Infection
Seroconversion
Verify with Western
Blot
ELISA
p24 capsid antigen
PCR
vRNA
Opportunistic Infections
PCP Cytomegalovirus Mycobacterium
Pneumocystis
carnii
Fungal: Protozoan: Viral:
Candidia T. Gondii Herpes
Systemic Isospora HSV-1, VZV, EBV
Neoplasms: Misc: Dz:
Lymphoid pneumonitis Pneumonia, GI,
Kaposi’s sarcoma brain, LN, blindness
Lymphoma
Treatment
Supportive Nucleoside Nonnucleoside
analogs that inhibitors of RT
interfere with
RT
Protease Entry inhibitors HAART:
inhibitors that interfere Highly Active
blocks cleaving with fusion AntiRetroviral
of proteins protein Therapy
HIV Animation for Drug Tx
http://www.hopkins-aids.edu/hiv_lifecycle/hivcycle_txt.html
HIV Poster of Life Cycle