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

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

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

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

Retrovirus

RNA

100-140nm

+ssRNA
5
9-10 KB

C D

gag pol env

RNA H
:
cDNA
Provirus


Human Immunodeficiency
Virus, HIV

1981 6 CDC 5 Los Angeles

CNS

Aquired Immunodeficiency Syndrome, AIDS

1983 1984 AIDS
Lymphadenopathy-associated virus LAV
T III Human T-lymphotrophic
virus type III HTLV-III AIDS AIDSrelated retrovirus ARV
1986 Human
immunodeficiency virus, HIV

 type

AIDS
70% HIV

HIV-1
HIV-2
HIV HIV-1

Viral genome

9.2kb +ssRNA with three structual

genes and six regulatory genes.

9.2KB

LTR
3 env pol gag
6 tat rev nef vif vpr vpu

Gene

Strucutre
Genes

Encoded
Protein

gag P24, p7
pol

Nucleocapsid

p17

Matrix

Reverse
transcriptase
Protease

Transcribes RNA genome

into DNA

Integrase

env

Function of Protein

gp120

Cleaves precusor
polypeptides
Integrates viral DNA into
host cell DNA
Attachment to CD40 protein

 Regulatory
Genes

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
Genes Protei
Function of Protein
n
Nef
Decreases CD4 proteins and class I
nef

vif

Vif

vpr

Vpr

vpu

Vpu

MHC proteins on surface of infected

cells
Important for pathogenesis by SIV
Stabilizes newly synthesized viral
DNA and transports core through
cytoplasm
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
HIV-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

HIV CD4
PHA 3
T
CPE

AIDS

7
56C30min 0.5%
10% 50% 35%
0.3%H2O2 5% 10min
68 C72h

WHO
100C 20min
20min

HIV AIDS

HIV 22%
72.4% AIDS HIV

10

AIDS

HIV 8-12 3-6

50-70%

6 -10

AIDS AIDS-related
complex, ARC

AIDS
Kaposi
Protozoal

pneumocystis
carinii now thought to be a
fungi toxoplasmosis, crytosporidosis

Fungal

candidiasis
crytococcosis , histoplasmosis, coccidiodomycosis

Bacterial

Mycobacterium avium complex ,

atypical mycobacterial disease ,
salmonella septicaemia ,
multiple or recurrent pyogenic bacterial infection

Viral

CMV, HSV, VZV, JCV

5
90%

Kaposis
Sarcoma

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

Pneumocystis
carinii

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

Candida Albicans

Candida infections are common with AIDS,

but most often appear as oral thrush, which
is a nuisance but not life-threatening.
Disseminated infections are uncommon, but
here is a rare Candida pneumonia, which
resembles a bacterial bronchopneumonia.

Clincal Response
Exposue
to HIV

No
infection

Persistent
generalized
lymphadenopathy

Infection

AIDSrelated
complex
AIDS

Acute
disease

Asymptomic
Neurological disease

Cell tropism: CD4+ T cells,

Macrophages
CD4+

HIV CD4+

cDNA
T HIV gp120
CD4
T

HIV
CTL
HIV
ADCC
HIV gp120 T MHC II
gp120 T
T

HIV B

CD4
HIV HIV
CPE
HIV

IL-2 -IFN

40%-90% AIDS
HIV
CNS

CD4+ T

ELISA
IFA

RNA

RIA
Western blot

PCR

HIV HTLV

Western blot

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

 : ORA HIV

HIV
20
HIV 1 2

10 15

FDA 2002
11

HIV AIDS

VIII

 HAART

2 HIV

Saquinavir Ritona
vir
HIV

8
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
2000

1. HIV1 Viral load > 1030000/ml

2. CD4 value < 250 cells/ml.
3. Full Blown AIDS .

100
40

80
30

60
20

40

10

20

2003

2002
40560 2001 32.0%
2001 2000
36.5% 2 639 ,
2001 65.6% 1 047

63.7% 25828 8.1

% 3292 9.3 %
3776
2002
100

2002

2002
9824
2001 19.5 %
2001 2000
58%
1045 2001 46.4%
363

HIV

2039

5.2 : 1
63.7%
8.1% 9.3%

70%

 18
1998 2

1350CC 304

15

1998-2010

2001-2005

22 11 6000

1998 12 1
2004:
2003 Live and let live ,

2002
Live, Let Live

2001
2000

1999 Listen ,Learn, Live!
--
1998 Force for Change:World AIDS
Campaign with Young People
--
1997 Children Living in a World with AIDS

1988 Join the Worldwide Effort

,
1989 Our Lives ,Our World --Lets Take Care of
Each Other
, --
1990 Women and AIDS

1991 Sharing the Challenge

1992 A Community Commitment

,
1993 Time to Act
,
1994 AIDS and the Family

1995 Shared Rights,Shared Responsibilities

,
1996 One World,One Hope
,

 T HTLV
Human T-Cell Lymphotropic
Virus

1978 T

C T
Human T-cell lymphotropic
virus, HTLV T
Human T-cell leukemia virus,
HTLV

T
HTLV II HTLV I
50%

100nm
gp120
p24 p18 LRT
HIV

I II T
40 T

RNA

IL-2 IL-2 CD4+

PHA
IL-2 36 C

(HTLV 1 specific antibody)

ELISA