1. HIV and the End of Optimism
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

2. 13.1: Overview June 5, 1981-immune deficiency reported in MMWR
Early 1980’s-acquired immune deficiency syndrome linked to a virus
Thought limited to male homosexuals. Haitians and heroin users-disease neglected
See-”And the Band Played On”

3. 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

4. Retrovirus “life cycle”
Reverse Transcription and integration are two key steps.
These two steps produce a form of the virus called the
provirus.

5. 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.

6. 13.3: Human Retroviruses-Timeline
 Year          Virus                 Event
 1980          HTLV-I              first human retrovirus-Gallo lab at NIH
 1981                                    first CDC report on AIDS (MMWR report)
 1982          HTLV-II             second human retrovirus-Gallo lab at NIH
 1983          LAV                   Montagnier lab in Paris isolates virus from pre symptomatic patient
1984          HTLV-III            Gallo lab isolates AIDS-related virus
 1984          ARV                  from San Francisco patient
 1985          LAV and HTLV-III are the same
SIV-mac           a primate retrovirus isolated from macaques
1986          HIV LAV/HTLV-III renamed HIV-1
HIV-2                West African species-from sooty mangabey monkeys

7. 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.

8. 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.
CCR5 is another important receptor; CCR5/delta32 mutation is a resistant form
HIV infection gradually wipes out the immune
system and allows opportunistic pathogens
to flourish.

9. 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

10. 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 HIV HIV-1
Zoonotic disease

11. Evolutionary Tree of SIV and HIV
HIV-2 in cluster with SIV-MM
HIV-1 in cluster with SIV-CPZ
Older tree-incomplete
Note HIV-1 Group M

12. Sources of HIV
8 groups of HIV-2: all from sooty mangabey 4 groups of HIV-1 3 from chimpanzee 1 from gorilla

13. 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?

14. 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.

15. Cut Hunter Simplest explanation “bushmeat” as food item
Bushmeat exposures to SIV not rare today
Blood contact during hunting or butchering

16. Geographic Source of HIV
SIV-cpz from southeast Cameroon most similar to HIV-1 M
Results from new technologies and many samples

17. When Did the “Jump” Occur?
“Molecular Clock” analysis
Includes newly discovered samples preserved since 1959 and 1960
Best estimate for jump is /- 20 years

18. How Did the New Virus Spread?
From Cameroon to European colonies in Congo Basin
Via river traffic
Reaches capital cities Brazzaville and Kinshasa (Leopoldville)

19. Spreads in capital cities
Rapid urbanization
Rail and river travel
Sex trade
Well-established by

20. Unsterile Injections But no way to sterilize syringes before reuse!
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!

21. Congo Independence Colonial infrastructure collapses UN peacekeepers
Humanitarian aid workers from Haiti
HIV returns with workers mid 1960s

22. 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