The Association of Epstein-barr Virus

8/19/2019 The Association of Epstein-barr Virus

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THE ASSOCIATION OFTHE ASSOCIATION OFEPSTEIN-BARR VIRUSEPSTEIN-BARR VIRUS

IN NASOPHARENGEALIN NASOPHARENGEALCARCINOMACARCINOMA

DYAH RATNA BUDIANIDYAH RATNA BUDIANI( DEPT OF PATHOLOGY ANATOMY/ BIOMEDICAL( DEPT OF PATHOLOGY ANATOMY/ BIOMEDICAL

LABORATORY SCHOOL OF MEDICINELABORATORY SCHOOL OF MEDICINE

SEBELAS MARET UNIVERSITY)SEBELAS MARET UNIVERSITY)


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• Pathmanathan et al. (1995) : mela!"#a$ a%a$&a

a'!'a' a$a"a EBV a%a NPC* Hal $ 'a$+a me$a"#

#a"e$a meml# ml#a' e"ae,# 'e"a #la".#a'

e$a$+ %ae"a e$%em#*

• Raab-Traub & Flyn (1986): $0a'0e NPC me$+a$%,$+

e'!me DNA EBV

• Yeung WM, et al. (1993). DNA EBV 'e1a"a '!"a%'

e"%'"2,'#a$ a%a in situ 1a"'$!ma $a'!.a"$+*

E!te"n-#arr $"ru! an% a!'aryngeal an*er


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EBV $.e1!$EBV $.e1!$ in vivoin vivo


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+*eat"* re!entat"'n ' "n"t"al e$ent! lea%"ng t' E#-"n%u*e%+*eat"* re!entat"'n ' "n"t"al e$ent! lea%"ng t' E#-"n%u*e%

tran!'rat"'n ' /uan #-*ell.tran!'rat"'n ' /uan #-*ell.


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E# 0EE+E# 0EE+ FT2FT2

E#41 Ma"ntenan*e ' $"ral gen'e "n %"$"%"ng '!t *ell

uregulat"'n ' R40-1 an%-e7re!!"'n

E#4 Fun*t"'nal ''l'g ' 't*: tran!a*t"$at"'n ' E# &*ellular gene! a*t"$ate! *-gr, "n%u*e0-01 tran!"t"'nt'geter "t E#4-;, "n%u*e! M;1 e7re!!"'n e!!ent"al'r #-*ell tran!'rat"'n

E#43a


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E#E#0EE+0EE+

FT2FT2

#/RF1 Fun*t"'naly an% !tru*turally ''l'g'u! t' b*l:"n"b"t a't'!"! %"!trub! %"erent"at"'n & "n%u*e!r'l"erat"'n "n e"tel"al *ell!

E#ER1


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+*eat"* rere!entat"'n ' E# R4 e7re!!"'n r'"le! "n %"erent E#-

"ne*te% #-*ell 'ulat"'n! "n t'n!"l! an% er"eral bl''%

' ealty E#-*arr"er! an% te"r r''!e% relat"'n!"


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+*eat"* rere!entat"'n ' E# R4 e7re!!"'n r'"le! "n %"erent

E#-"ne*te% #-*ell 'ulat"'n! "n t'n!"l! an% er"eral bl''% '

ealty E#-*arr"er! an% te"r r''!e% relat"'n!"*

a"$e #-*ell! are "ne*te% by E#-$"r"'n! tat enter te 'r'aryngeal

ly n'%e! by *r'!!"ng e"tel"al barr"er!. E# gly*'r't*"n g35

b"n%! t' te re*et'r A1 re!ent 'n all #-*ell!. n%er "nluen*e '

A1-tr"gger"ng an% te !ub!eBuent E#4-%r"$en tran!*r"t"'n

r'gra, na"$e #-*ell! %"erent"atC "nt' # bla!t! tat e7re!! te ull

!et ' latent E# R4! an% "* are r'bably *'ntr'lle% by ant"-E#

*yt't'7"* T-*ell re!'n!e!. Te # bla!t urter %"erent"ate! tr'ug

te ger"nal *enter $"a *entr'bla!t t' *entr'*yte. #'t *ell tye!

e7re!! te latent ebrane r'te"n! M;1 an% M;, "* r'$"%e!

te "t gr't an% !ur$"$al !"gnal! "n ab!en*e ' ant"gen, an%E#42 "* "! e!!ent"al 'r a"ntenan*e ' te $"ral gen'e "n te

'!t *ell. F"nally, %"erent"ate% E#-"ne*te% *ell, enter te *"r*ulat"'n

"t! e'ry #-*ell!, tat are generally !"lent 'r $"ral R4 e7re!!"'n

but :ay '**a!"'nally e7re!! M; R4 (Ar +. +te$en! "!

a*=n'le%ge% 'r r'$"%"ng t"! "gure).


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;at'gen"* ee*t!;at'gen"* ee*t! E# gene r'%u*t re!'n!"bleE# gene r'%u*t re!'n!"ble

Inhibition of apoptosis

M""*="ng #*l- un*t"'n

regulat"'n ' #*l-regulat"'n ' 4

Genetic instability

;a!!"$e "n%u*t"'n ' tran!lat"'n.

4*t"$e "n%u*t"'n ' tran!l'*at"'n $"a R40-1


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ter E# gene!

E# 0EE+E# 0EE+ FT2FT2

#+MF1 4T24TE+ 0EE ED;RE++2 ;+T-TR4+R2;T24Y

E4-A(#MRF1) 4T24TEA #Y ?ta a!!'*"te! "t E# A4 ;'lyera!e

#4F5 A4 ;YMER4+E

#4F M4R A4 #2A20 ;RTE2

#DF1 T/YM2A2E >24+E

#F1 0;35;RTE2

#0F5 4>42E EDE4+E


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• 3e'e"$ 1!,$"e' (a$$,al $1%e$1e : 4*51a'e'/ 644*4444*

• S!, a'a/ N!" A."1a G"ee$la$% a$%

Ala'#a m!"e a$ 75 /644*444

EBV $ NPCEBV $ NPC


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EBV $ NPCEBV $ NPC

• Te a!!'*"at"'n ' E# 'n =erat"n"!"ng*ar*"n'a (W/ 22) an% art"*ularyun%"$erent"ate% !ub tye(W/ t"e 222) "! elle!tabl"!e%.

• +all r''rt"'n ' +Bua'u! *ar*"n'a(W/ t"e 2) : u!"ng ;R %ete*t"'n $"ralA4.

• +Bua'u! *ell! ; "! aear! t' !'

ge'gra"*al $ar"ab"l"ty.• Re*ent !tu%y : +''="ng an% 'r "ne*t"'n

/;! "gt be "n$'l$e% "n at'gene!"! '!Bua'u! *ell! ;.


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• augan et al : !'="ng a! a r"!= a*t'r 'r!!* ;! but n't 'r n'n-=erat"na!"n"ng*ar*"n'a.!"ng ;R(/'r%"ng et al ) %ete*te% /; A4

"n !'e ++ tat er E# negat"$e.• Ra!e= et al : 'un% E# an% /; A4 by

;R "n 88 an% 53 ' ;( all /; '!"t"$e*a!e! ere al!' E# '!"t"$e )

• Ten%en*y : /; G un%"eren*"ate%*ar*"n'a an% /; - ++ ;!


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ED;RE++2 F E#4! & M;! #ED;RE++2 F E#4! & M;! #

ly'a!ly'a! r'$"%e! "n%"*at"'n! ' b"'*e"*al!r'$"%e! "n%"*at"'n! ' b"'*e"*al!

e*an"!! : "n r"ary # y'*yte gr't.e*an"!! : "n r"ary # y'*yte gr't.

e7re!! 'n an 'r un* 'n ! ' u a e y


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e7re!! 'n an 'r un* 'n ! ' u a e y

0ene Fun*t"'n Relat"'n "t E#

2n $"tr';53 T,m!" ',"e''!"

+e$e 8*ell *y*le *e*='"ntH

B1l-7 I$2' a!!''

A74 I$2' a!!''

1-.+" P"!e$ &"!'$e #$a'e1-m&1 Cell P"!l.e"a!$

R2 T,m!" ',"e''!"

+e$e9 B$%$+ ! E7F

"e0e$' e$"& ! S

a'e*IL-64 B-Cell "!l.e"a!$9

$2!$ !. l!1al

mm,$e "e'!$'e

P"!e$ 2!,$% 2& EBNA-LP

U"e+,lae% 2& LMP6

U"e+,lae% 2& LMP6

U"e+,lae% 2& EBNA7U"e+,lae% ,!$ EBV $.e1!$*

B!,$% 2& EBNA-LP

U"e+,lae% ,!$ EBV $.e1!$*


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0ene Fun*t"'n Relat"'n "t E# in vivo

;53

#*l-

4

*-gr

*-y*

Rb

IL-64

T,m!" ',"e''!"

+e$e 8*ell *y*le *e*='"ntH

I$2' a!!''

I$2' a!!''

P"!e$ &"!'$e #$a'e

Cell P"!l.e"a!$

T,m!" ',"e''!"

+e$e9 B$%$+ ! E7F

"e0e$' e$"& ! S

a'e*

B-Cell "!l.e"a!$9

$2!$ !. l!1al

mm,$e "e'!$'e

I$ HD : $!$e

U"e+,lae% $ PLTD

I$ HD : $!$e

I$ HD : $!$e9 U"e+,lae% $ PLTD ARL*

I$ HD : $!$e

U$#$!$

U"e+,lae% $ EBV ;HD

'ne : n' %"ern*e! 'un% 'r E#G an% E#- *a!e!


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EBVEBVmal+$a$'


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A!!'' a$% "!l.e"a!$ 1!$"!l A!!'' a$% "!l.e"a!$ 1!$"!l

M;1M;1

4;;T+2+


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4;;T+2+

S+$al$+ aa& .!" TNFR-1 (55 #Da) a$% TNFR-2 (=5 #Da) !11,"' 2& e

"e1",me$ !. 'e0e"al a%ae" "!e$' ! e $"a1ell,la" "e1e!" 1!mle>* Omal

'+$al$+ a10& "e?,"e' "e1e!" "me"@a!$* TNFR-6 $all& "e1",' TRADD

(TNFRa''!1ae% %ea %!ma$) a$% $%,1e' a!!'' "!,+ e a1!$' !.

"!e!l&1 e$@&me' #$!$ a' 1a'a'e' a aa& 'a"e% 2& a$!e" "e1e!"#$!$ a' CD5 (Fa')* CD5 a$% TNFRI !''e'' 'mla" $"a1ell,la" 'e?,e$1e'

#$!$ a' %ea %!ma$' (DD) a$% 2! "e1", e 'ame a%ae" "!e$' #$!$ a'

Fa'-a''!1ae% %ea %!ma$ (FADD) 2e.!"e a10a$+ 1a'a'e-* TNFR-6 al'!

$%,1e' a!!'' 2& a10a$+ 1a'a'e-7 "!,+ e "e1",me$ !. RIP ("e1e!"

$e"a1$+ "!e$)* RIP al'! a' a .,$1!$al 1!m!$e$ a 1a$ $ae NF-B a$%

1-,$ a10a!$ 2! .a0!"$+ 1ell ',"00al a"*C "!$.lamma!"& .,$1!$'* TNFR-7

la1#' a DD 1!m!$e$ 2, "e1",' a%ae" "!e$' #$!$ a' TRAFI a$% TRAF2

(TNFR-a''!1ae% .a1!") a $e"a1 RIP ! me%ae NF-B a$% 1-,$ a1

0a!$* TRAF7 al'! "e1",' a%%!$al "!e$' a a"e a$a!!1 #$!$ a' IAP

($2!"' !. a!!'' "!e$l* DED, %ea e..e1!" %!ma$9 RAIDD, RIP-a''!1ae%

ICH-6-l#e "!e$ %ea %!ma$ 1 a10ae' "!a!!1 1a'a'e'9 MEKKl,m!+e$-a10ae% "!e$/E"l1 #$a'e #$a'e-69 INK, 1-,$ N-e"m$al #$a'e9 NIK, NF-

B-$%,1$+ #$a'e9 6->B/NF-B $a10e 1!mle> !. NFB a 2e1!me' a10ae%

e$ I-B !"!$ ' 1lea0e%* (A%ae% ."!m L$ e al*& e"m''!$*)


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The Association of Epstein-barr Virus