Understanding Microorganisms

Subject 1

AIDS
1

 What is AIDS?

What is AIDS?
?

Acquired Immune Deficiency

Syndrome

What is HIV?
HIV ?

Human Immunodeficiency
Virus

Symptoms of AIDS

1.Kaposi's Sarcoma
2.Pneumonia
Opportunistic infection
s

Opportunistic Infection

Disease
Normal microbial flora
Weak immune function
Old age
Long illness
Organ-transplantatio
n
AIDS
Kaposi's Sarcoma

Kaposi's Sarcoma

Main symptom of AIDS

Purple patches
Human Herpes Virus VIII (HHV8)
Three types
Classical type
occurs on the leg of the ol
d
Organ transplant type
AIDS type

Kaposi's Sarcoma
7

Pneumonia

Common symptom of AID

S patients.
Pneumocystis jiroveci
Fungus
Human lungs
Opportunistic infection

Pneumocystis jiroveci
8

 History of AIDS

History of AIDS

Pneumonia
In 1981 in the United
States
Drug users & homosexual
men
Kaposi's sarcoma
Many gay men
CDC task force
The 4H disease (Haitians,
homosexuals,
hemophiliacs, and heroin
users)
GRID (Gay-Related
Immune Deficiency)

Weekly Report in 1981 on

"AIDS"

10

The Morbidity and Mortality Weekly

Report

11

Who Identified HIV ?

HIV ?

Dr. Luc Montagnier

Dr. Robert Gallo

12

Conflict on HIV
Identification HIV

Luc Montagnier

Robert Gallo

Lymphadenopathy-Associat
ed Virus (LAV)

Human T-Lymphotropic Vir

us type III (HTLV-)

in May 1983

in Aprill 1984

Pasteur institute in France

National Cancer Institute in

US

applied patent
The first discovery of HIV

applied patent
Mass production of the viru
s

13

Conflict on HIV
Identification HIV
Dispute occurred
1. Honor between two persons
2. Patent between two nations
for royalty of AIDS diagnosis

14

Conflict on HIV
Identification HIV

They came together, but lost chance to win the Nobel prize togeth
er.
15

 Transmission of AIDS

16

Three Routes of AIDS

1. Sex
Semen and vaginal fluid
2. Blood
Hemophiliac

Blood transfusion
blood products
Thermal treatment needed
3. Vertical transmission
Pregnancy, Delivery, Feedi
ng
17

Act Risk

Exposure route
Blood transfusion

90 %

Childbirth (to child)

25 %

Needle-sharing injection drug use

0.67 %

Percutaneous needle stick

0.30 %

Receptive anal intercourse*

Insertive anal intercourse*

0.03 %
0.050.30 %

Insertive penile-vaginal intercourse*

0.010.38 %

Insertive oral intercourse*

0.043.0 %

Receptive penile-vaginal intercourse*

Receptive oral intercourse*
*

Chance of infection

00.04 %
00.005 %

assuming no condom use

source refers to oral intercourse performed on a man
18

AIDS Cases

19

AIDS Patients

, ?
Contact is safe.
Handshakes
Swimming
Drinking water in the same
cup
Using things together
Sneeze, cough are safe
No virus in tears, sweat, &
saliva
No transfer through
mosquito

20

Annual Cases (US)

Incubation
Time = 10
years

21

AIDS Worldwide (2007)

22

AIDS Epidemic (2002)

70% of AIDS in southern Africa

23

AIDS Epidemic

24

 SIV : Origin of HIV

25

HIV-1, HIV-2
HIV

HIV-2
West Africa in 1985
Milder disease
HIV-1
99% of global AIDS cases
9 subtypes
A, B, C, D, F, G, H, J, K, N,
O
15-22% difference

26

HIV-1 Subtypes
HIV-1

B subtype : common among homosexuals

(30% of black homosexuals in U.S)

27

SIV

Simian Immunodeficiency Vir

us
Simian

Similar to HIV
infects Monkey, Chimpanzee
18 species

28

Phylogenetic Tree of HIV

HIV SIV

GGGAX
GGGXX
GXXXX

GGGAA

HIV-1

GGGAG

SIV-1

GGGCC

SIV-2

GCCTT

SIV-3

29

Phylogenetic Tree of HIV

HIV SIV

(Mangabey
monkey)

(Chimpanze
e)

30

Superinfection in Chimpanzee

Two different SIV

Red-headed Mangabey monkey SI
V
Spotted nose monkey SIV

The genomes of two different SIV viru

ses were mixed.

New Chimera SIV in chimpanzee body

(Superinfection)

Infects humans (HIV)

31

Research on Chimpanzee

99% genome similarity

Comparing genome
No AIDS in Chimpanzees
No Malaria in Chimpanzees

32

AIDS Day

No AIDS cure
Prevention is the best way!!
Condom
Day of AIDS Prevention in 19
88

33

 Replication of HIV

34

Animal RNA Virus

Influenza

SARS

HIV

35

Retrovirus

Central Dogma
Genetic information is in DNA
1 DNA 100 RNA 10,000 Protei
ns
Exception : Retrovirus
Retro = back
Genetic material is RNA
1 RNA 1 DNA 100 RNA

DNA

RNA

Protein
36

(gp120)

Retrovirus
1. Reverse
transcriptase

2. Integrase
3. Protease

37

T Lymphocyte
HIV

Helper T lymphocyte
HIV attacks
Helper T = TH
Reduction of T lymphocyte
s
Immunodeficiency

T lymphocytes under HIV attack

38

If HIV infects TH lymphocytes

Macrophage

B Lymphocytes B

1. Does not make

antibodies
2. The wrong
Antibodies to
bind to normal
cells

Helper T
Lymphocytes
T

1. Decreased the
preying ability of
the viruses and
bacteria
2. Are infected with
HIV around the
whole body HIV
transmission
Natural Killer
Cell

1. Ability to kill
cancer cell39

Docking Site of HIV

HIV

gp120
CXCR-4
(CCR5)

CD4

T lymphocyte cell
(Target cell)
40

Docking Site of HIV

Nucleocapsid

T lymphocyte cell
(Target cell)

Nucleocapsid is inserted into

the cell.
41

42

Replication Process

Reverse
transcriptas
e
Integrase

Protease

43

HIV Release

HIV T

A matureed
form of HIV

A budding
HIV virus
44

The Cell Numbers

T

1L T

Normal
600~1200 (perL)
Treatment needed
<350
Opportunistic infecti
on
<200

Treatment
Infection

45

3 Steps in AIDS Progression

HIV
RNA
TH lymphocyte
1. After infections, intense immune
response
Decreased helper T cells,
HIV decreased after increasing

2. Incubation
Increasing
HIV

3. Opportunistic
infection
Death

46

Monitoring of HIV
HIV

47

 HIV Inhibitor

48

HIV Inhibitors

49

HIV Inhibitors

50

Nevirapine

Non-Nucleoside Reverse
Transcriptase Inhibitor
(NNRTI)
Nevirapine
binds directly to the
catalytic site of HIV
reverse transcriptase
inhibits elongation of the
nucleotide chain.
51

Azidothymidine

Nucleoside Reverse
Transcriptase Inhibitor
(NRTI)
Azidothymidine (AZT)
Zidovudine
The most successful agents
Nucleoside analogs
chemically related to
thymidine
No 3-hydroxyl group

52

Saquinavir, Indinavir
,

Proteinase inhibitors
effective for treatment of
HIV
binding HIV protease

Saquinavir

inhibiting processing
large viral proteins

Saquinavir or Indinavir
Protease inhibitor

Indinavir

Peptide analog
53

 Cocktail Therapy

54

Reverse Transcriptase

Accuracy of Genome Replicatio

n
Very high (Human)
Very low (HIV)

Reverse transcriptase
RNA DNA
Low Accuracy
Rate = 10 / 10,000 (bp)
Easy resistance to drug

The copy machine is problematic !

55

Cocktail Therapy

Treatment with multi HIV drug

s
By Dr. David Ho
No resistance to all drugs simu
ltaneously

56

Dr. David Ho

Time magazine's 1996 Man of the Y

ear is AIDS researcher Dr. David Ho.
"cocktail" of HIV inhibitors
in early stages of infection

57

Result of Cocktail Therapy

After six months of treatment, no HIV virus was dete

cted in the bodies of 80% of patients treated.

Earvin Johnson Jr. (a basketball

star)

58

Limits of Cocktail Therapy

1. HIVs are different

2. Expensive ($20,000/year)
5% patients use
3. Not be supplied enough
18~19 inhibitors,
10 cocktail therapies in US
2~3 inhibitors,
only 1 cocktail therapy in Afri
ca
59

Limits of Cocktail Therapy

4. No penetration of drug
Hiding place
Immune cell nucleus
Central nervous
system
Reproductive organs
Lymph node
AIDS became a chronic
disease that a continuous
treatment is needed.

60

Delta32 (CCR5)
32

Delta32 gene

gp120

Macrophage receptor
(CCR5)
strong immunity to HIV

CD4

10-15% of Europeans
No black African

CCR5
61

62