MICROBIOLOGY PPT LECTURE NOTES | Karya Tulis Ilmiah

Retrovirus

R e tr o v ir id a e
R N A t u m o r v ir u s g r o u p
O n v ir in a e

RNA 含含含含含含

R o u s s a r c o m a v ir u s
M u r in e s a r c o m a v ir u s
M o u s e m a m m a r y t u m o r v ir u s
M a e d i/ V is n a g r o u p
L e n t iv ir in a e

含含含含含

H IV I, H IV II
S h e e p v is n a v ir u s
E q u in e in f e c t io u s a n e m ia v ir u s
F o a m y v ir u s g r o u p
S p u m a v ir in a e


含含含含含含

H u m a n f o a m y v ir u s

Retrovirus
含含含含含含 RNA 含


含含含含含含含含








含含含 100-140nm 含含含含含含含含含含含
含含含含含含含含含 +ssRNA 含含 5‘ 含含含含

含含含含含含含含 9-10 KB 含含含含含含含含含含
含含含含含含含含含含含含含含含含含 C 含含 D 含含
含含含
含含含含含含含含含含含含含含含含
gag 含 pol 含 env 含含含含含含含含含含含含

含含含含含含含含含含含含含含含 RNA 含 H
含含含含 : 含含含含含含含含含含含 cDNA 含含含
含含含含含含含含含含 Provirus 含



含含含含含含含含含含含含含含


含含含含含含含

Human Immunodeficiency
Virus, HIV


含含含含




1981 年 6 年年年 CDC 年年年年年 5 年年 Los Angeles 年年年年年年年年年年年年
年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年
年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年
CNS 年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年年
年 Aquired Immunodeficiency Syndrome, AIDS 年
1983 年年 1984 年年 AIDS 年年年年年年年年年年年年年年年年年年
年 Lymphadenopathy-associated virus 年 LAV 年年年年年 T 年年
年年年年 III 年年 Human T-lymphotrophic virus type
III 年 HTLV-III 年年 AIDS 年年年年年 AIDS-related
retrovirus 年 ARV 年年年年年年年年年年年年年年 1986 年年年年年年年年年年年年年
年 Human immunodeficiency virus, HIV 年

含含含 type 含





含含含含含含含含含 AIDS 含含含含含含含含含含含含含含含含含 70%
含含含含含含含含 HIV 含含含
HIV-1 含含含含含含含含
HIV-2 含含含含含含含
含含含 HIV 含含含 HIV-1

Viral genome


9.2kb +ssRNA with three
structual genes and six
regulatory genes.



含含含含含 9.2KB

含含含含含含含含含含含 LTR 含

3 含含含含含含 env 含 pol 含 gag 含
6 含含含含含含 tat 含 rev 含 nef 含 vif 含 vpr 含 vpu 含

含含含含含 Strucutre Genes 含
Gene

Encoded
Protein

gag P24, p7
pol

Function of Protein
Nucleocapsid

p17

Matrix

Reverse

transcriptase
Protease

Transcribes RNA genome
into DNA

Integrase

Integrates viral DNA into
host cell DNA

env gp120

Cleaves precusor
polypeptides

Attachment to CD40 protein
Fusion with host cell

含含含含含 Regulatory Genes 含

vif viral infectivity factor
tat transactivating protein
vpu viral protein U
rev regulator of virion protein
expression
nef negative regulatory factor

Regulatory Genes Found in HIV
That Are Required for Replication
Gene Protein

Protein Function

tat

Tat

Activation of transcription
of viral genes


rev

Rev

Transport of late mRNA
from nucleus to
cytoplasm

Regulatory Genes Found in HIV That
Are Not Required for Replication
Gene Protei
Function of Protein
s
n
Nef
Decreases CD4 proteins and class I
nef

MHC proteins on surface of infected
cells

Important for pathogenesis by SIV

vif

Vif

Stabilizes newly synthesized viral
DNA and transports core through
cytoplasm

vpr

Vpr

vpu

Vpu

Transports viral core from cytoplasm
into nucleus in nondividing cells

Enhances virion release from cell

Replication

Viral dynamics in a
typical HIV+ person[1]
•Error frequency in RT: 3 x 10- 5 per base per
replication cycle
•HI V-1 genome is composed of 104 = 10,000
nucleotides
•up to 10 billion viruses are produced daily
•100 million new cell infections/ day
•10 million viruses per day with one new "error"
(mutation)

HIV env genetic subtypes (1998)

Adapted from
J. Mullins


年年年年




HIV 含含含含含含含含含含含含含含含含 CD4 含含含含含含含含含含含含
PHA 含含 3 含含含含含含 T 含含含含含含含含含含含含含含含含含含含含
含含含 CPE 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含
含含含含含含含含
含含含含含含含含含含含含含含含含含含含 AIDS 含含

含含含含含含


含含含含含
• 含含含含含含 7 含
• 含含含 56C30min 含含含含含含含含含含含含 0.5% 含含含含含 10%
含含含含 50% 含含含 35% 含含含含 0.3%H2O2 含 5% 含含含
10min 含含含含含含
• 含含含含含含 68 C72h 含含含含含含含含含含含



WHO 含含含
100C 20min
含含含含含含含 20min

年年年年年年年年


含含含
HIV 含含含含 AIDS 含含
含含含含含含含含含含含含含含含含含含含含含含含



含含含含
含含含含
含含含含含含含含含含含含含含含含
含含含 HIV 含含含含 22% 含含含含
含含 72.4% 含 AIDS 含含含含含含含含 HIV

含含含
含含含含



含含含含
4 含含含含含含
含含含含 10 含
含含
含含含含
含含含含
含含含含含
含含 AIDS



年年年年
• HIV 含含含含含含含 8-12 含含含含含含含含 3-6 含含含含含含含含 5
0-70% 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含
含含含含含含含含含含含含含含含含含含含含含含含



年年年年
含含 6 含 -10 含含含含含含含



AIDS 含含含含含含含 AIDS-related complex,
ARC 含
含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含




含含 AIDS 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含
含 Kaposi 含含含
含含含 Protozoal 含


含含含含含含含含 pneumocystis carinii 含 now
thought to be a fungi 含含 toxoplasmosis,
crytosporidosis

含含含 Fungal 含


含含含含含含含含 candidiasis 含含含含含含含含含含 crytococcosis 含 ,
histoplasmosis, coccidiodomycosis

含含含 Bacterial 含


含含含 Mycobacterium avium complex 含 , 含含含含含含含含
含 atypical mycobacterial disease 含 , 含含含含含含
含 salmonella septicaemia 含 , 含含含含含含含含含含含含含 multiple
or recurrent pyogenic bacterial infection 含

含含含 Viral 含




CMV, HSV, VZV, JCV

含含含含含含含含含含含含含含含含含 5 含含含含含含含 90%

Kaposi’s
Sarcoma



With
dissemination to
extrapulmonary
sites,
Pneumocystis
carinii tends to
produce foci with
prominent
calcification, as
seen in the kidney
here grossly



With giemsa stain
at high
magnification, the
faint bluish dotlike intracystic
bodies of
Pneumocystis
carinii in lung are
seen in this
cytologic
preparation from a
bronchoalveolar
lavage

Pneumocystis
carinii

Candida Albicans

Candida infections are common
with AIDS, but most often
appear as oral thrush, which is a
nuisance but not lifethreatening. Disseminated
infections are uncommon, but
here is a rare Candida

Clincal Response
Exposue
to HIV

No
infection

Persistent
generalized
lymphadenopathy

Infection

AIDSrelated
complex
AIDS

Acute
disease

Asymptomic
Neurological disease

年年年年







Cell tropism: CD4+ T cells,
Macrophages
含 CD4+ 含含含含含
含含含含含含含含含含含含含含含含含
含含含含含含含含含含含
含含含含含含含

HIV 含 CD4+ 含含含含含


含含含含含含含含含含含含含含含含含含含含含含含含含含含含



含含含含含含含含 cDNA 含含含含含含含含含



含含 T 含含含含含 HIV gp120 含含含含含含含含含 CD4 含含含含
含含含含含含含含含含含含含含含含含含含 T 含含含含

含含含含





含含含含含含 HIV 含含含含含含含含含含含 CTL 含含含含含含含含含
含含含含含含 HIV 含含含含含含含含含含含含含含含含含 ADCC 含含
含含
HIV 含 gp120 含 T 含含含含含 MHC II 含含含含含含含含含
含含含 gp120 含含含含含含 T 含含含含含含含含含含含含含含含含含
含含 T 含含含含含含含含含含

年年年年年年年年年


HIV 含含含 B 含含含含含含含含含含含含含含含含含含含含含含含含含
含含含含含含含含含含含含含含含含含含含含含



含含含含含含含含含含含含含含含 CD4 含含含 HIV 含含含含含含含含
含含含 HIV 含含含含含含含含含含含含含 CPE 含含含含含含含含
HIV 含含含含含含含含含含含含含含含含含含含含含含含含含含



含含含含含含含含含 IL-2 含 -IFN 含含含含含含含含含

含含含含含含含




含含 40%-90% 含 AIDS 含含含含含含含含含含含含含 HIV 含含
含含含含含含含含含含含含含含
含含含含含含含含含含含含含 CNS 含含含含含含含含含含含含含含含含含含
含含含含含含含含含含含含含含含含含含含含含含

含含含含含含含含含


CD4+ T 含含含含含含含含含含含含含含含含



含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含
“含含含”含含



含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含

含含含含含含


含含含含
• 含含

ELISA
IFA



RIA
Western blot

含含 RNA
PCR



含含含含含

HIV 含含含含含含含含含含含含 HTLV 含含含含含 含含含含含含含含含含含含含含含含
含含
含含含含含含 Western blot 含含

ELISA for HIV antibody
Screening tests should be as sensitive as possible

Microplate ELISA for HIV antibody: coloured wells indicate reactivity

Western blot for HIV antibody
Confirmatory tests should be as specific as possible


There are different criteria
for the interpretation of HIV
Western blot results e.g.
CDC, WHO, American Red
Cross.



The most important
antibodies are those against
the envelope glycoproteins
gp120, gp160, and gp41



p24 antibody is usually
present but may be absent
in the later stages of HIV
infection

含含含含 : ORA HIV


含含含含含含含含含含含含含含含含含含 HIV 含含含含含 20 含含含含含
含含含含含
 含含含含含含含 HIV 含含含含含含 1 含 2 含含含含含含含含含含含含含含含含含
含含含含含含含含含含含
 含含含含 10 含 15 含含



含含含含含含含含含含含 FDA 含含含含 2002 含 11 含含含含含含
含含含含

含含








含含 HIV 含含含 AIDS 含含含含含含含含含含含含含含含
含含含含含含含含含含含含含含含含含含含
含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含
含含含含含含
含含含含含含含含含含含含 VIII 含含含
含含含含含含含含含含
含含含含含含含含含含含含含含含含含含

年年年年年年年年年 HAART 年






含含含含含含 2 含 HIV 含含含含含含
含含含含含含含含
含 Saquinavir 含 Ritonavi
r 含含含含含含含含 HIV 含含含含含含
含含含含含含含含含含
含含含含含含含含含含含含含含含含含含
含含含含含含
含含含含含含含 8 含 RMB

Highly
Active
Anti-Retroviral Therapy
 HAART: Two
nucleoside analog RT
inhibitors and 1
protease inhibitor
 Now also: Two
nucleoside analog RT
inhibitors and 1 non
nucleoside

HAART 含含含含含 2000 含
1. HIV1 Viral load > 1030000/ml
2. CD4 value < 250 cells/ml.
3. Full Blown AIDS ….

40

A ID S m ortality and
protease inhibitor (P I) use

100
80

30

60
20

40

10

20

0

0

含含含含含含含含含含

含含含含

2003 含含含含含含含






含含 2002 含含含含含含含含含含含含含含含含含 40560 含含含 20
01 含含含含含含 32.0% 含含含含含含含含含含含含含 2001 含含含
2000 含含含含 36.5% 含含含含含含含含含 2 639 含 , 含 20
01 含含含含 65.6% 含含含 1 047 含
含含含含含含含含含含含含含含含含含含含含 63.7% 含 25828 含含
含含含含含含 8.1 % 含 3292 含含含含含含含含含含含含 9.3 %
含 3776 含含
含含含含含含含含含含 2002 含含含含含含含含含含含含含含含 100 含含
  

2002 含含含含含含含含



2002 含含含含含含含含含含含含含含
含含含含含含含 9824 含
• 含 2001 含含含含 19.5 % 含含含含含含含含含含含含含 200
1 含含 2000 含含含含 58% 含
• 含含 1045 含含含 2001 含含含 46.4%
• 含含 363 含

HIV 含含含含含含含含







含含含含 20—39 含含含
含含含含含含含
含含含含含 5.2 : 1
含含含含含含含含含含含含含含含 63.7% 含含含含含含含含含 8.1% 含
含含含 9.3% 含
含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含
含含含含 70% 含含含含含含含含含含含 含
含含含含含含含含含含含含含含含

含含含含含含 18 含含含含含含含含含含含含含含含含含含含含含含含含含 19
98 含 2 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含
含含含含含含含含含含含含含含含含含含含含含含含 1350CC 含含含含含含含
304 含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含
含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含
含含含含含含含含含含含含含“含含含含含含含”含含含含含含含含含含“含含含含
含”含含含含含含含含含含含含含含含含含 15 含含含含含含含含含含含含含含含含
含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含

含含含含含含含含含含含含含

年年




《含含含含含含含含含含含含含含含含 1998-2010 含含》
《含含含含含含含含含含含含含含含 2001-2005 含含》
含含含含含《含含含含含含含含含含含含含含含含含含含含含含含含
》 《
》 《
含》含含含含含含含含含含含含含含



年年





含含含含含含含含含含含含
含含含含含含含含含含含
含含含含含含含含含含含
含含含含含含含含含

• 含含含含 22 含含含含含 11 含含含含含含含含 6000 含含含含





含含含含含含含含含含含含含含含含含含含
含含含含含含含含
含含含含含含含含含含含含含含含含含含含含含含含含含含含含

含含含含含含含含含含含




含含含含含含含含
含含含含
含含含含含含含含含含含















含含含含含含含 1998 含 12 含 1 含
2004:“ 含含含含含含含含含”含
2003 含“ Live and let live”“ 含含含含 , 含含含含”含
2002 含
• Live, Let Live
• 含含含含含含含含含含含含含含含含含含含
2001 含含含含含含含含含含含含含含含
2000 含
• 含含含含含含含含含含含含含含含含
1999 Listen ,Learn, Live!
含含含含含含含含含含含 -- 含含含含含含含含
1998 Force for Change:World AIDS Campaign
with Young People
含含含 -- 含含含含含含含含含
1997 Children Living in a World with AIDS
含含含含含含含含含含含含含



















1988 Join the Worldwide Effort
含含含含 , 含含含含
1989 Our Lives ,Our World --Let‘s Take Care of
Each Other
含含含含含 , 含含含含含 -- 含含含含含含含
1990 Women and AIDS
含含含含含含
1991 Sharing the Challenge
含含含含含含含含含含
1992 A Community Commitment
含含含含含 , 含含含含含含
1993 Time to Act
含含含含 , 含含含含
1994 AIDS and the Family
含含含含含含
1995 Shared Rights,Shared Responsibilities
含含含含 , 含含含含
1996 One World,One Hope
含含含含 , 含含含含

含含含 T 含含含含含 HTLV 含 Human
T-Cell Lymphotropic Virus

年年




1978 含含 T 含含含含含含含含含含含含含含含含含含含含含
含含含含含含含含含含含含 C 含含含含含含含含含含含含 T 含含
含含含 Human T-cell lymphotropic
virus, HTLV 含含含含 T 含含含含含含含含 Human
T-cell leukemia virus, HTLV 含
含含含含含含含含含含含含含含含含含含含含含含含含 T 含含含含
含含含含含 HTLV II 含含含含含含含含 HTLV I 含含含含
含含含含含 50% 含含含

含含含含含



含含含 100nm 含含含含含含含含含含含含含含含含含含含
gp120 含含含含含含含 p24 含 p18 含含含含含含
LRT 含含含含含含 HIV 含含

含含含




含含含含含含含含含含含含含含含含含含含含含含含含含含含含含含
含含含含含
I 含含 II 含含含含含含 T 含含含含含含含含含 40 含含含
含含含含 T 含含含含含含含含含含含含含含含含含含含含含含含含
含含含含含含含含含含含含含含含含含含含含

含含含含


含含含含含含含含含含 RNA 含含含含含含含含含含含含含含含
含含含含含含含含含含含含含含含含含含含含含含含含含含含含
IL-2 含含含含 IL-2 含含 CD4+ 含含含含含含

含含含含含


含含含含含含含
• 含含含含含含含含含含含含含 PHA 含含含含含 IL-2 含含 3—6
含含含含含含含含 C 含含含含含



含含含含 (HTLV 1 specific antibody)
• ELISA
• 含含含含含含