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14,000 people in the world are infected with HIV each day

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Title: 14,000 people in the world are infected with HIV each day


1
14,000 people in the world are infected with HIV
each day
What percentage of these people are in your age
group (15-24 year olds)?
2
HIV and AIDS
Brian J. Rybarczyk, PhD University of North
Carolina-Chapel Hill brybar_at_med.unc.edu
3
Objectives
  • Define the functions of the three HIV enzymes
  • Describe HIV interactions with immune system
  • Scientifically argue pros and cons of anti-HIV
    therapies
  • Analyze impact of AIDS epidemic socially
    scientifically

4
Overview
  • HIV is a lentivirus
  • Relatively long incubation period
  • Genome is composed of 2 ssRNA
  • Associated with immune suppression

5
Key to HIV Infection
HIV attacks the immune system, the same system
that is supposed to protect the body from invaders
6
(No Transcript)
7
nucleocapsid
gp120
gp41
RNA genome
integrase
reverse transcriptase
protease
8
Origins of HIV?
Human Error Oral Polio Vaccine (OPV) development
in Africa, 1950s (disproved, Nature 407 (6801)
p.117, 2000). The River Ed Hooper
Natural Transfer SIVcpz was transferred to humans
during contact hunting accident, butchery, pet
bite, etc.
www.weber.ucsd.edu/jmoore/publications/HIVorigin.
html
9
Modes of Transmission
10
Mother to Child Transmission
  • Transmission may occur either in utero or
    during or after delivery
  • Successful treatment Nevirapine (NNRTI), 4
    per one time administration immediately prior to
    delivery. 50 decrease in transmission

11
Factoids about HIV/AIDS
Life span of plasma virions 8 hours
Duration of HIV lifecycle 1.2 days
Average total HIV production 1 x 1010 virions
per day
How many virions go on to productively infect a
cell?
Perelson et. al. Science 271, p.1582-5, 1996
12
Video Demonstrations
Portrait of the Virus Lifecycle of HIV Bodys
Defense and Host Response
13
General Responses to HIV Infection
Cellular
Humoral
Cell destruction of infected cells
Neutralizing antibody production B-cells
Cytotoxic T Lymphocyte (CTL response) Natural
Killer cells, CD8 and CD4
14
CTL Response to HIV
Cytotoxic T-Lymphocytes
Need to lyse and destroy infected cells before
infectious progeny virus can be produced
CD8 and CD4 lymphocytes respond to the
presentation of (HIV-specific) epitopes in
association with MHC I and II molecules
15
antigen
Antigen Presenting Cell
Cytotoxic T-cell
16
Acute
Asymptomatic
AIDS
Level of immune response or viremia
60
10
Years
Days
1
0
17
Humoral Response
Anti-HIV antibodies produced in response to
foreign antigens Env, core proteins
Neutralizing antibodies against gp120 (env)
(V1-V3 regions of env)
Env changes amino acid sequence thus altering
effectiveness of neutralizing antibodies viral
escape
18
Current Research
1) Determine changes in V1/V2 region of SIV env
during infection characterization of viral
variants 2) Using gene arrays to evaluate host
response during infection
19
Rhesus macaque
20
HIV Envelope Protein
21
Heteroduplex Tracking Assay
22
Intrarectal challenge
probe
E660
41 wk
2 wk
8 wk
23
Intravenous challenge
probe
41 wk
E660
2 wk
8 wk
24
Neutralizing antibodies are correlated with V1/V2
diversity
25
Sequences pre- and post- Td50
IV
IR
26
How do we inhibit/treat HIV infections?
27
Approaches to anti-HIV Therapy
Virus Entry Neutralizing antibodies, CD4
analogs, T-20
Early Steps prior to integration AZT, ddI,
nucleoside analogs, anti-integrase, interferons
Anti-Infected cells - CD8 cells, antiviral
antibodies
Vaccine development prime and boost
28
HIV lifecycle and anti-retrovirals
29
Question Why arent current drug treatments
curing HIV infection?
The virus mutates in response to drug treatments
over time, allowing certain forms of the virus to
persist and reinfect (virus develops drug
resistance) HIV evades the immune system
30
HAART Highly Active Anti-Retroviral Therapy
Administer combination of anti-retroviral drugs
Combination of 2 nucleoside analogs and a
protease inhibitor to target multiple sites of
HIV infection Found to be more effective than
treating patient with only one drug at a time
31
Majic Johnson
From an immunological standpoint, why doesnt
Majic Johnson have AIDS but is still HIV positive?
32
What is a Vaccine?
Introduction of antigen (viral components) that
can elicit an immune response
Preventing HIV infection requires recognition of
virus-infected cells as well as free virions
33
Ideal Vaccine
  • Elicits neutralizing antibodies reacting with
    all HIV strains
  • Induces cellular and humoral responses
  • Does not induce autoimmune responses
  • Induces local immunity at all sites of HIV
    entry
  • Safe, no toxic effects
  • Long-lasting effect

34
Approaches to Vaccine Development
  • Whole-killed (inactivated) virus
  • Live (attenuated) variants
  • Subunit vaccine envelope glycoproteins
  • Viral proteins in live vectors combination of
    live viral genes with HIV structural genes
  • DNA vaccines

35
Vaccine Development Why has it been difficult
to develop a vaccine?
  • No clear protective immunity even after natural
    infection
  • Virus is highly variable
  • Virus is able to escape immune response
  • Can infect different cell types
  • Virus attacks immune cells themselves
  • No perfect animal model

Science 291 1686-1688, 2001
36
Two Sides of the Coin
Prevention vaccine development to prevent HIV
infections from occurring
Treatment helping those already infected with
the disease be able to maintain a healthy
lifestyle and to control virus replication and
effects on host. (reservoirs of virus)
37
Summary
  • HIV is a retrovirus that infects CD4 T cells,
    dendritic cells, and macrophages integrates into
    host genome using RT
  • Most individuals infected with HIV progress to
    AIDS
  • HIV accumulates many mutations during infection
    and drug treatment is followed by outgrowth of
    drug-resistant variants
  • An immune response controls but does not
    eliminate HIV
  • HIV infection leads to low CD4 T cells,
    increased susceptibility to opportunistic
    infection, and eventually death

38
Questions for Further Thought
What are the mechanisms involved that appear to
protect some people from infection and not
others? What determines the different rates of
progression to AIDS after infection?
(Progressors vs non-progressors) If HIV can no
longer be detected in a person, can that person
be considered cured?
39
Testing
  • Student Health Services on campus
  • Free HIV testing, UNC- Pembroke, April 17, 2002
  • UNC-Chapel Hill
  • Free blood test
  • 40 OraSure
  • NC Department of Health and Human Services
  • 1-800-HIV-TEST (www.homeaccess.com)

40
Other Movies of Interest
  • Philadelphia Tom Hanks
  • In The Gloaming
  • Love, Valor, Compassion Jason Alexander
  • My Own Country Marissa Tomei
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