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 22.5.08 - 8
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 22.5.08 - 8
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Human Herpes Viruses
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 22.5.08 - 8
14
( , DNA - .,
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 22.5.08 - 8
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 22.5.08 - 8
16
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 22.5.08 - 8
17
Herpesviruses
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 22.5.08 - 8
18
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 22.5.08 - 8
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 22.5.08 - 8
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 22.5.08 - 8
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 22.5.08 - 8
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 22.5.08 - 8
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 22.5.08 - 8
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 22.5.08 - 8
28
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 22.5.08 - 8
29

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 22.5.08 - 8
30
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 22.5.08 - 8
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 22.5.08 - 8
32
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 22.5.08 - 8
33
, , uncoating .
RNA - DNA DNA - . "
,RNaseH - RNA - .DNA DNA -
.dsDNA - , DNA -
. DNA - .
. DNA "
. " .DDRP
LTR - dsDNA - :U3,R,U5 -
U3 - .
U3 - R- ) (DDRP
. , .
R - U5- poly A- .
" , LTR -
) DNA -(
, DDRP - .DNA -
.5'- DDRP - poly A- . ,
DDRP - Poly A- ,
poly A- , . , mRNA - :
.R-U5-gag-pol-env-U3-R
LPR - , .
, LPR -
.
.DNA -
. . SRC - . -
.acute .
.c-sis -
. c-sis - 95%- .PDGF -
.
) :(slow
. , .
. .v-onc " ,
. .
, . ,
.
DNA - , .
DNA - , .southern blot -
,
. .
in vitro .?
, .
" cis .
DNA - . .insertional mutagenation
:
promoter insertion ,
down stream . ,
.
promoter - . LTR -
. LTR -
.
) enhancer insertion ( . ,
,
. up stream down stream

 22.5.08 - 8
34
. LTR -
. .
,trans )
.(trans
) :(acute
.v-onc ,
,
" .
.? .
.
. v-onc -
) (slow
.
, .
, .
,
. .
. ,
.acute - . . messenger
,
DNA - . . DNA
. , . .acute
,
.in vitro
HTLV1
) ( .Th ,
.HTLV1 . 1% ,
1- 1,700 - . "
, .HIV - . .
HTLV - .
,T :
,HTL -
. , ,
. , ,in vitro . ,

. .
HTLV - .PX
:
TAX - .
LTR - . .
.
.T
REX . RNA - .
4 .
TAX - LTR - .
.trans trans -
T .T-
, . , -
,DNA .
CREB - CPB , CREB -
. , , CPB

 22.5.08 - 8
35
p53 - .E47 - , p53- , .
:
IL2 .IL2 -

T.
NF-kB .T

.T " .IkB TAX -

. , NF-kB - .
,T TAX . TAX - IL2 - .
. . TAX -
.NF-kB - , ,
)(
.TAX crisis ,
. .
, ATL -
.((adult T lymphoma .

 22.5.08 - 8
36
DNA

, - .15- -
20% . ,
.
.
-
, .
.
,
, tumor suppressors .p53

- -
.
, ,
) ( . ,
-
- ,
.
? , .
,
. -
) ( , -
.
,
. ,DNA -
) EBV ,(HHV-8- , .B RNA -
- - ,human T cell leukemia virus -
C .
DNA- ):(RNA
,DNA ,
RNA . ,
-
- DNA
) (
,
) (.
,
. ,
- , )
( - . , .

. , ,
. - .
100 ) , ( .
50% - .
- .
, .
-
, ,
- epidermodysplasia veruciformis -
) (UV .
.

 22.5.08 - 8
37
,
- (low risk type (HPV 6,11
, ) (HPV 16,18 - high risk type -
.
. HPV
. ,
) (.
:HPV DNA , E early
- genes , L .
E5, E6 - E7 - ,DNA
. - E1 ,
E2 E4 ,
" .
) (,
. , ,
)
50 ( -
. - maintenance DNA replication
. -
-
. DNA - -
,DNA
. , E6 E7
DNA . DNA -
, -
DNA .

 22.5.08 - 8
38
DNA
- Human papilloma virus
.
E2 ,
- E6 E7- .DNA
, .
E1 ,E2 -
E6 E7 - .E2 , E2
- .,
E6 E7-
DNA , .
.
- .
, , -
- .
E5 .
, -
.
E6 E7 - .
,tumor suppressor genes -
, -
. .,
E7 ,tumor suppressor RB - , ,cyclin-CDK
. E6 ) p53
, p53 ,(p53
. ,bak
HDLG ) contact
(inhibition . E6 E7- "
) "high risk "low risk"- ( p53 . RB -
. E6
.telomerase .
E5 ,
. E5 , ,
-
.
HPV - " "high risk - ,
. ,
E6 E7 - - - "
) , , '(.
) high risk - low risk-( -
) viral
,(like particles .
(Epstein-Barr Virus (EBV
Burkitt Lymphoma, -
,nasopharyngeal carcinoma B
.Hodgkin Lymphoma
:Burkitt Lymphoma B , ,
)
( , ,EBV
.EBNA1
EBV - -
; ) ,EBV nuclear antigens

 22.5.08 - 8
39
(LMP1
.
, , EBNA1
,
- .
burkitt lymphoma , , 15%
) 98% - ( .
- 8 - c-myc
) .(2 ,22 ,14
8 - c-myc
, - c-myc
. , ,
.
- EBV
EBV - .
, B EBV - .,
B
.
,
-
,
, . , .
, -
.
, - LMP1
)
,TNF - -
- NFB
(.
:Nasopharyngeal carcinoma .
) ( , EBNA1
,LMP1 - .
- , )
( , HLA .
- .
.IgA
, B -
- . ,
)
(.
B
,B ,
. ,
, 85% - .
.
, - ) ,(aflatoxin B1 '.
,
- .
B , , , ,
.x-protein x-protein - -
)- ( ,

 22.5.08 - 8
40
. "
. - ,
, ) (
.
, .
, -
) ( , tumor suppressor
.
,
.
.
C )
(.
Kaposi's sarcoma virus
.spindle cells ,
.
- ) ( , ) (,
) ( , ) (.
,HHV8
body cavity lymphoma) Castleman's Disease - - -
( . , :
Kaposi sarcome ;
Kaposi Sarcoma ; )
" (.
- Kaposi's sarcoma - DNA
, herpes virus
.saimiri , )
v , - (vCyclin ;
) ( ;
. ,
,
.

 22.5.08 - 8
41
HIV - Human Immunodeficiency Virus
, HIV , ,Lentiviruses -
- ,
T . D-
) type ( )
(.
: HIV - HIV1 - HIV2 - 40% -
, HIV2 .,
HIV - (reverse transcriptase (RT-
) 5 - ( , -
12-15 .HIV2
clades
20-30% - , clade
- . , HIV1 -
N ,O- .
: HIV - - .
,RNA ) mRNA (
) RNA - ( . RNA -
, RT, integrase) protease -
( . , )
.(accessory proteins - ,p24
.(p17 (matrix protein -
gp120 - surface protein ,-
gp41 -
. ,
gp" ) gp "
, ( .
, MHC.
: , " RT -
.dsDNA DNA - ,
DNA - (LTR (long terminal repeats
. )
(lentivirus :
(gag (group specific
.RNA -
pol - RT, integrase ,.protease -
env gp120.gp41 -
, ) - (accessory genes

) ( . ,
.
HIV2 , vpx vpu .HIV1 -
.
mRNA -
. , gag -
55kD " p17, p24
p6 .p7 - 160kD "
, gp160 ER -' "
. .
western blot
.

 22.5.08 - 8
42

rev . tat- ; nef
; vif, vpr, vpu -vpx-
. vif - ; vpr
DNA - , vpu - .
:tat ,
. DNA -
LTR - ) '5-
- (
RNA . , RNA -
stem&loop RNA polymerase II ,
RNA . tat tar ,
) cyclin T, CDK9( -C - II
. 1,000
, . ,
- ,
, , Kaposi sarcoma
.
:rev
. RNA -
: mRNA ) (9KB
) ,(pol ,gag RNA - ,
mRNA 4KB .env ,
mRNA ) rev, tat
,(nef - , mRNA -

. rev , mRNA
- RNA - rev regulatory element
) (env mRNA - .
, .
:nef ,
. , :
.CD4 .
,
, . nef
. , co-receptor - .
down regulation MHC class 1
" .
nef -
.
. nef -
,
) , (.
17 .

:
,CD4 - CD4
) ( . -
-
CD4 - .
- - ) - CCR5
,(R5 T- ) - CXCR4
.(X4 , ,dual trophic -

 22.5.08 - 8
43
T ) T ,CCR5
R5 (.
- - :
" ) ( ,
.
, ,
.T - 5-6
, 90% - ) ( .
T ) (,
.
: gp120 , ,CD4 -
- . , gp41
, .
. , ,
reverse transcription - dsDNA LTR . vpr
) ( DNA -
, integrase dsDNA - .
, " RNA .II T
, T
NFB .
RNA ,tat
. , mRNA
, rev mRNA
. , RNA ,
, ER - gp .
,
. ,
gag pol - .

HIV ) ,(Acquired immune deficiency syndrome

- . - TH
,
- .
:delayed type hyper sensitivity - . ,
.
: , .
,gp CD4
- . T
, gp120-
.CD4 -
, .anergy
,CD4 .
- ,
. )
( , .
: "
.
, -
. -
BBB , "
) (tat .
.

 22.5.08 - 8
44
: -
) 4-8( , ) 12( ,
- )
( . ,T
- )
( ) ( ,
. , CTL
- .
) ,( , ,
, . ,
, T- ,
.
,CD4 .
- , ).(flu-like
) -
,equilibrium ( , T
, -
. ,
. ,
.
, ,
,
. CD4 ) 500 ,(l- full
- blown disease " ) ,,
( ) .(38
500 - ,l- full blown
200 .l- - aids related complex ,
. ,
) (
HIV -.
: ,gp
-
.RT ,
- gp " . , gp
.
; ) ,
(; T ) (;
;MHC class 1 FAS ligand
CTL .FAS
: - ,
, .
ELISA
. ,
.false positive , -
:western blot ) - , ,(
, - gagenv-
. , PCR RNA
DNA - ,
. ,
) (.

 22.5.08 - 8
45
- : ,
. ) (
- RT
)( .
RT - )
( , RT - )
( . .47
-
. ) Highly active
(antiretroviral therapy, HAART
,
.
: , .
,
.
.

 22.5.08 - 8
46

.
, .
.
, , ) .(1000
.
:Antigenic drift 3 , ,HA
.
:Antigenic shift ,
reassortment
, .
. .
Mis-sense .
. ,
- . , , ." -
. , , .

 22.5.08 - 8
47

. .
.
, .
. .
.
' . -
-
- . -
proof reading . .
.

.
. .
.
, , .
: ..
- attachment - .
,cd4 .cd4
HIV - . -
. cd4 .
g120 "G
.g120
gp41 : , ' .-
T -
HIV - .

.HIV ,
downregulation .
.
.
, .
,
HIV , .HAART -
gp120 .gp41 - ,HIV - .
, 33 , gp41 .
. '.
:uncoating - -
, . 3 .Vp1 2 3 vp1
meristic acid , uncoating .
, displacement
. '
,vintropans .
:
. RNA .
.HA, NA, M2 ,M2 ion channels .
, pH .

* . *.
M2 . pH -
. .uncoating - 2
- m2 . .
CDC .

 22.5.08 - 8
48
- , " .
3 - .1 : .2 , .3 , .
, "
, . .
" " .
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. DNA RNA
- . ,
, .
, .
) ( 2
.
- .
.acyclovir - .
. 3 .

OH .
.
"" ganciclovir OH . ,CMV - ,
, . , 30
. , .
DNA - .
:
. ,
,
. .
, , , .
- AZT ) ,(RT - .
. .

.
- -
.Idoxuridine " DNA - "
DNA . . chain
,termination , unstable base pairing
. .
.
- Brivudin -
.
-
- , .
,
.AZT .
"
. RNA -
." RNA.
, AZT
.AZT - -
.
DNA -
, .
. ..

 22.5.08 - 8
49
- ribavirin - .
, in vitro .vivo - mRNA -
7 . prime cap 5 - .
, . CAP
.
RNA .
:
. "
" . Raltegravir
.HIV
:cleavage -
, " .
,autocleavage
.
HIV . ,HAART. HIV aspartyl
HIV - .
HIV ,
. .
" : 3 -
.HIV . .HIV -
, .
.
: .
.
.
- tamiflu .
: .
HAART -
. 2 , ,
. AZT
. .
16 RNA - ."
, .
-
- .
.
: ' , .
.