Transcript Set 13 HIV - IUP Personal Websites

Emerging Diseases
Lecture 13:
HIV and the End of Optimism
13.1: Overview
13.2: HIV is a Retrovirus
13.3: Human Retroviruses
13.4: Targets of HIV-1
13.5: Antiviral Therapy
13.6: Origins
13.1: Overview
June 5, 1981-immune deficiency
reported in MMWR
Early 1980’s-acquired immune deficiency
syndrome linked to a virus
1983-virus isolated in France
1986-virus named HIV
Thought limited to male homosexuals.
Haitians and heroin users-disease
neglected
See-”And the Band Played On”
13.2: HIV is a Retrovirus
RNA virus that works in
reverse
Viral RNA is copied over
into DNA
Reverses the usual direction
of copying
Retrovirus “life cycle”
Reverse Transcription and integration are two key steps.
These two steps produce a form of the virus called the
provirus.
Provirus
•
•
•
•
•
•
DNA copy of retrovirus RNA inserted into host DNA
Behaves exactly like a regular gene.
When active, produces more viral particles.
Can cause mutations that lead to cancer.
May be passed on through sperm and egg DNA.
Endogenous retroviruses are the ones that
you inherit from your parents.
• Most retroviruses are benign and do not cause
disease.
13.3: Human Retroviruses-Timeline
Year
Virus
Event
1980
1981
1982
1983
HTLV-I
1984
1984
1985
HTLV-III
ARV
first human retrovirus-Gallo lab at NIH
first CDC report on AIDS (MMWR report)
second human retrovirus-Gallo lab at NIH
Montagnier lab in Paris isolates virus from presymptomatic patient
Gallo lab isolates AIDS-related virus
from San Francisco patient
LAV and HTLV-III are the same
a primate retrovirus isolated from macaques
LAV/HTLV-III renamed HIV-1
West African strain-from sooty mangabey monkeys
1986
HTLV-II
LAV
SIV-mac
HIV-1
HIV-2
13.3: Human Retroviruses
Both HIV-1 and HIV-2 are classified as lentiviruses (a
type of retrovirus) because it takes so long for their
symptoms to appear.
HIV-2 is “weaker” than HIV-1 and is mainly confined to
West Africa.
The worldwide epidemic is caused by one group of HIV-1.
All other HIVs are primarily African diseases
Both are transmitted via body fluids; blood-borne or
sexual.
13.4: Targets of HIV-1
Receptor = molecule that virus
attaches to
CD4 Protein = primary
receptor for HIV-1
CD4+ cells = cells that have
the CD4 protein on their
surface
T cells, nervous system cells,
other immune system cells.
Opportunistic pathogens kill
when immune system
declines.
HIV infection gradually wipes out the immune
system and allows opportunistic pathogens
to flourish.
CCR5 is another important
receptor; CCR5/delta32
mutation is a resistant form
13.5: Antiviral Therapy
• Virus mutates rapidly to become resistant to
standard antiviral medications because
reverse transcription is error-prone.
• No one anti-retroviral (ARV) drug can hold the
virus in check for long.
• Combination therapy-the use of several
classes of drugs at once-works better.
• HAART-Highly Aggressive Anti-Retroviral
Therapy
13.6: Origins of HIV
• HIV is closely related to viruses found in other
primates: SIV
• The chimpanzee version of SIV (SIVcpz) is
closest of all to almost all
HIV-1
• Zoonotic disease
Evolutionary Tree of SIV and HIV
• HIV-2 in
cluster with
SIV-MM
• HIV-1 in
cluster with
SIV-CPZ
• Older treeincomplete
• Note HIV-1
Group M
Sources of HIV
8 groups of HIV-2: all from
sooty mangabey
4 groups of HIV-1
3 from chimpanzee
1 from gorilla
SIV jumped into humans at least 12 times to
become 4 groups of HIV-1 and 8 groups of
HIV-2
But only one of the zoonotic viruses (the M
group of HIV-1) spread around the world.
What happened?
Ideas About the Origins of HIV and
How it Spread
Cut Hunter-came from wild animal contact via
bushmeat- a “natural transfer”
Heart of Darkness- brutal colonial regimes
disrupted societies and spread disease
Used Needles-spread by western medical
procedures in colonial Africa
Probably a combination of all is correct.
Cut Hunter
• Simplest explanation
• “bushmeat” as food
item
• Bushmeat exposures
to SIV not rare today
• Blood contact during
hunting or butchering
Geographic Source of HIV
• SIV-cpz from
southeast
Cameroon most
similar to HIV-1
M
• Results from new
technologies and
many samples
When Did the “Jump” Occur?
• “Molecular Clock” analysis
• Includes newly discovered
samples preserved since
1959 and 1960
Best estimate for jump is 1910 +/- 20 years
How Did the New Virus Spread?
• From Cameroon to European colonies in
Congo Basin
• Via river traffic
• Reaches capital cities Brazzaville and Kinshasa
(Leopoldville)
• Spreads in capital
cities
• Rapid
urbanization
• Rail and river
travel
• Sex trade
• Well-established
by 1959-60
Unsterile Injections
• Reusable syringes available by
1930
• Mass injections against sleeping
sickness, malaria, other diseases
• Sex workers required to be
examined at clinics
• Vaccines, antibiotics
But no way to
sterilize syringes
before reuse!
Congo Independence
• Colonial infrastructure
collapses
• UN peacekeepers
• Humanitarian aid workers
from Haiti
• HIV returns with workers mid
1960s
Spread to US and beyond
• Via blood products (the
Vampire of the Caribbean)
• Sex tourism
• Likely introduced by one
person
• Almost all infections outside
sub-Saharan Africa traceable
to this one transfer
• There probably was a Patient
Zero-but not Gaetan Dugas