Y HQC VlgT NAM THANG 6 - S6 1/2011 Ngo Thj Thuyen ( 2 0 0 4 ) , "Khao sat tinh hinh
thai phu nhiem HIV/AIDS tat benh vien phu san tmng Udng tir 1/2000 den 9/2004". Lu$n van thac syyhoc.
Do Thj Thu Thuy, Nguyen Thj Mai Anh (2008), "Tinh hinh lay truyen HIV tCi" m? sang con tai Benh vien Phu san Hai Phong giai doan 2004- 2008", Tap chl Hdi nghi San Phu khoa Viet-Phap- 3/2009, tr 18-24.
Mayaux M J . j j e g l a s J.P., Mandelbrot L., et al (1997), "Acceptability and impact of zidovudine forprevention of mother to child human immunodeficiency virus 1 transmission tn France", -7 fla//a/r, 131:857-62,
Mrus 3.M., Goldie 5.J., Weinstein M.C., Tsevat J (2000), " The cost-effectiveness of elective cesarean delivery fiar HIV infected woman with detedableHIV RNA during pregnancy", AIDS, 14(16) :2609-2610.
SO SANH CHU5l GEN EBNA-1 VIRUS EPSTEIN-BARR CHUNG S I VA HH2 CUA VIET NAM vein MOT SO' CHUNG TRUNG QUOC VA THE Gidl
Hodng Thj Minh C h S u * , Vu Thi T i e n * , Nguyen Dinh P h u c * * va Le Thanh H d a * TOM TAT
Ooan gen EBNA-1 (dSu cudi 30 cd dO dlii 0,765 WJ cua hai chung S I (ttj" mau benh pham cua benh nhan nhap vidn thanh phd Hd Qif Minh) va HN2 (Ha Noi) dutfc thu nhan bSng PCR va giai trinh tU trUc tiep.
Truy cSp Ngan hang gen cho thay, toan bo 765 bp cua chung SI hoan toan ddng nheft (100%) vdi chuoi EBNA-1 cua Chung GDI (AY961628, Quang Dong, Tmng Qudc). Trinh t u nucleotide va amino acid ciia SI va HN2 dutfc so sanh vdi mpt sd chung the gidi la GDI (Trung Qudc), B95-8 (chung cd dien, co 2 chuoi gen), C18 (Tmng Quoc), JF2 (khdng ro xuat xu) va AG876 (Ghana). Ket qua cho thay, SI va HN2 c6 mu'c dp dong nhSt (identity) den 99% ve nucleotide va 99 - 100% ve amino acid vdi chung GDI. Cac chiing ciia the gidi (B95-8, ca 2 loai; AG876; CIS va JF2) co t / le ddng n h ^ (nucleotide) va tUdng ddng (amino acid) thap hdn rat nhieu (chi cd 90 - 97%, lan lUdt) khi so sanh vdi cac chiing cua Viet Nam. Phan tich pha he dyS tren dD" lieu gen EBNA-1 cung xac djnh phan nhom cua SI va HN2 cung vdi chiing GDI phan lap t^i Quang Oong (Trung Qudc). Nhu* vay, hai chiing SI va HN2 CO d^c diem thanh phan gen va quan he pha h§
gan gui vdi chiing GDI, ddng Quang Ddng, ma dong nay dudc chimg minh gay ung tJiU vom hong (NPC) rat cao, dieu dd canh bao nguy cd nay tai Viet l^lam.
Tiyichda-. Ep^ein-Barr; EBNA-1; tJPC; ddng nhat;
tutfng dong; pha he; tien tnen ung thu".
SUMMARY
COMPARATIVE ANALYSIS OF EBNA-1 OF EPSTEIN-BARR VIRUS BETWEEN THE VIETNAMESE S I AND H N 2 I S O U T E S AND THE
CHINESE/GLOBAL STRAINS A portion of EBNA-1 (3' end) of 0.765 kb for SI (from
* Vien Cong nghe sinh hgc; **TrWdng D^i hgc Y Hd Ngl Phan bl4n khoa hoc: GS.TS. Ddl Duy Ban
a patient admitted in a hospital in Ho Chi l^inh city) and HN2 (Hanoi) isolates was obtained using PCR and sequencing. Searching in GenBank revealed, that the 765 bp EBNA-1 nucleotide sequence of SI is completely identical to ttiat of the GDI {AY961628, Guangdong, China) isolate. Nulceotide and amino acid sequence of SI and HN2, respectively, was aligned with GDI (China), B95-8 (classical strain, both variants), C18 (China), JF2 (unknown) and AG876 (Ghana). Results revealed, SI and HN2 showed 99%
identity and 99 - 100% homology, respectively, to those of the GDI strain. The global isolates (B95-8, both variants; AG876; C18 and JF2) have mu'ch lower identity (nucleotide) and homology (amino acid), 90 - 97%, respectively, compared to the two isolates of Vietnam. Phylogentic analysis based on the EBNA-1 data also revealed that the two isolates of Vietnam (SI and HN2) was grouped with the GDI of China. This indicated that the SI and HN2 have genetic and phylogenetic properties related to the GDI, Guangdong lineage of China, of which the tendency to nasopharyngeal carcinoma tumorigenesis was very high. This give rise to warning that an NPC-group of EBV emerged in Vietnam with the high risk of NPC pathogenesis.
Keywords: Epstein-Ban-; EBNA-1; NPC; identity;
homology; phylogeny; tumorigenesis.
I. DJ^T V A N o i
Epstein-Barr virus (EBV) Ja Herpesvirus thuoc type 4, nhdm Gamma, hp Herpesviridae, gay nhiem tren 90% dan sd the gidi. Nhiem EBV thdng thuSng khong gay trieu chOrng gi, tuy nhien, sau khi bien ddi te bao, EBV Id nguyen
Y Hpc VI$T HAM THANG 6 • S61/2011 nhan lien quan den mot loat cdc benh ly nghiem
trong, bao gom ung thu vom - mui - hpng (NPC, nasopharyngeal carcinoma), ung thu' lymphoma Hodgkin (HD, Hodgkin's lymphoma), ung thu lymphoma Burkitt (BL, Burkltt's lymphoma), posttransplant lymphoma, hairy leukoplakia v^
nhieu loai khac (Raab-Traub, 2002). EBV c6 vai tro djch t l hpc cong dong quan trpng do truyen nhiem gSy bdnh trdn ngi/dl, lan truyen qua dildng tieu h6a va thifdng dupe phit hl?n trong chat thii te bao, chat tiet d phSn tren cua he tieu hoa va ho hap nhU nUdc bpt, niem djch vung hpng (Cheng va cs, 2002).
He gen cua EBV co 6 tS hpp gen ma h6a cho cac ioai protein khang nguyen: Khing nguySn nhan, ky hieu la EBNA: (EBNA-1, EBNA-2, EBNA- 3A, EBNA-3B, EBNA-3C v i EBNA-LP) va 3 gen ma hoa cho protein ming (LMP-1, LMP-2A v i LMP-2B) (l^uray. Young, 2001; Cohen, 2006). Gen EBNA- 1 la vung DNA nSm trong td hpp gen EBNA ma hoa cho protein EBNA-1, co tac dung bam vao DNA. Protein EBNA-1 chju vai tro thiet yeu trong qua trinh xam nhap v i nhan len, cung nhu duy tri su tai tao he gen cua virus (Chou v i cs, 2008). Gen EBNA-1 v i sin pham protein EBNA-1 CO mat trong tat ca mpi dang khol u co lien quan den EBV; co khi nang bleu hien protein bang each sil dung mpt trong 4 loai promoter khdi dpng (Cohen, 2006; Nguyen Oinh Phuc v i Le Thanh Hoa, 2008). EBNA-1 cua chung cS dien 695-8 la chuoi polypeptide bao gom 641 amino add, trong do tiiinh phan 3 amino acid glycine- glydne-alanine (Gly-Gly-Ala) duHc lap lai nhieu lan, ma so lupng lip thay doi khac nhau trong cac mlu/chung EBV khac nhau (All v i cs, 2009). Vj tri amino add 487 cho phep xac djnh phan t^p cua EBV, cho den nay, tai Viet Nam mdi phat hipn 3 phan typ l i P-ala, P-thr va V-val trong so 5 phan typ cua the gidi (Le Tlianh Hoa v
Viet Nam la mpt nUdc nSm trong vung chju anh hudng cua djch te hpc til cac nude trong vung, d3c biet l i inh hudng tU phutJng Bac, EBV cd mUc dp truyen lay v i dien tien kha phitc tap v i dong Quang Oong co mu'c dp dien Hen ung thU vom NPC rft ac liet (Do va cs, 2008; Nguyen Oinh Phuc v i LS Thanh Hda, 2008). Thu thap mau b^nh pham cua benh nhan NPC tU cac vung dja ly khac nhau (tij' 3 mien: BSc, Trung, Nam), phan lap diuol gen v i giii trinh tU de xem xet cau tnJc phan tU cua gen EBNA-1, tU do so sanh doi chieu cau true phan til EBV Viet Nam vdl the gidi l i mot npi dung quan trpng nham xac djnh blen doi di truyen
100
lien quan den djch te hpc phan tiir cua cic chiing npi dja giy benh, dong thdi, co dUpc dii' lieu gen v i h$ gen cua loai virus niy tai Viet Nam de so sinh vdi EBV cua the gidi.
Trong bil bio niy chiing tdi gidi thieu ket qui phin lap doan gen d dau 3' ciia EBNA-1 chiing SI (fp Ho Chi l^inh) v i HN2 (Hi Npi) cua Vi^t Nam, xac djnh cau trtic phan tii* va so sanh vdi mpt so chiing ciia Trung QuSc v i the gidi.
H. NGUYlN V&T LifU VA PHUONG PHAP 2.1. Mau b#nh phSm
Bpnh pham d^ng mau md tUPi thu bing phUPng phap sinh thiet (biopsy), bao quin d - 20''C trong diiu kiSn an toin sinh hpc cao. Mlu thu tU b^nh nhin nhap vien tai Hi Npi, ky hieu la HN2; va tU benh nhan nhap vien tai thanh piio Ho Chi Minh, ky hieu l i SI.
2.2. Tich chiet DNA tong sS Chiing toi sil dung kit tach chiet DNA ciia hang BIONNER (Hin Quoc). Tdm tat nhu sau:
nghien mau thinh huyen dich; cho proteinase IC, li v i cho RNase. Cho dung mdi GC, li d 70'^ roi cho Isopropanol, ly tam de thu djch. Chuydn len cpt Ipc, ly tam, loai bd djch dUdi. Cho dung mSI W l , ly tam, bd djch dudi. Cho dung mdi W2, ly tim, bd djch dudi. Diuyen cpt sang 6ng Eppendorf mdi, cho djch tich EL ly tam, thu djdt bin dudi l i DNA tong so ciia mau, bio quan d - 20°C. Kiem tra DNA bang di$n dl tren th^di agarose 1%, nhupm ethidium bromide. DNA hien thi l i vach sing d^t tieu chuan de thUc hien PCR 2.3. Thiet ke moi cho EBNA-i, thurc hi|n PCR, giai trinh t ^ va phan tich so lieu
Doan gen EBNA-1 (khoing 0,76 kb) thu dupe bing PCR vdl khuon l i DNA tong so,- sijr dung cip moi; EBKIF: 5' GTCATCATCATCCGGGTCTC 3' va EBVR: ? CGATTGAGGGCGTCTCCTAAC 3'.^Sin pham PCR dupe glil trinh ti/ trUe tiep. Chuoi gen dulje tfiu nhin sau khi giii trinh tiT, dUpe xU ly bSng ChUdng trinh SeqEdl.03, sip xep I>in9 AssembiyLIGNl.9 v i MacVector8.2 (AaKliys Inc.) d may tinh Macintosh, so sanh ddi dii&i bing chuUng trinh GENEDOC2.5 bang miy tinli PC. Thinh phan amino acid dupe thu nhan bang each sil dung bp ma ciia vi sinii vat bac thap (vl khuan, bacterial code) co trong Ngan hing gen.
Phin tich phi h# bing chUdng trinh MEGA4.0 (Tamura v i cs, 2007).
Y HQC VIET NAM THANG 6 - SO 1/2011 III. KET QUA VA BAN LU$N
3.1. Thu nhSn chuSi nucleotide va xac djnh cSfu true gen EBNA-1
Tu' benh pham dang mau mo tUdi thu bSng phUdng phap sinh thiet ciia mau so HN2 va SI, chung toi tien hanh tach DNA tong so, thUc hi?n PCR, tach dong va giai trinh tu". Ooan gen EBNA-1 thu dUdc bdi cap moi EBKIF-EBVR cd kich thUdc co djnh la 765 bp, ma hoa cho 254 amino acid. Ca hai chiing ciia Viet Nam deu cho san pham EBNA-1 [a 765 bp, chu'ng to khong co bat ky dot bien them-bdt (in-del mutation) trong vung gen nay, nhUng cd mdt so dot bien diem (point-mutation).
Chiing toi sir dung chuoi nucleotide ciia mot chung Viet Nam (chung SI) de lam dff lieu truy cap Ngan hang gen. Ket qua trinh bay d Bang 1.
Bang 1. Ket qua truy cap Ngan hang gen su* dung chuoi gen EBNA-1 ciia chung SI (TP Ho Chi Minh, Viet Nam) (765 bp)
So ding ky ftY961628.3 FJ710109.1 V01555.2
|AY192024.1 IA1507799.2
|U02455.1 1U02454.1
|U02428.1 M80517.1
1
^279927.1 IAY825078.1 U21197.1
Mo ta chuoi dicti thu nh$n 6Uifc Human herpesvirus 4 strain GDI, complete genome Cloning vector pPAC7, complete sequence Epstein-Barr virus (EBV) genome, strain 895-8 BAC cloning vector pEBAC190G, complete sequence Human herpesvirus 4 complete wild type genome
f>l«m
1410 1343 1343 1343
Piem cao n h » 1410 1343 1343 1343 1343 111343 Qoning vector rpDI^, complete sequence 111343 |]1343 Cloning vector pCMVEBNA, complete sequence
Cloning vector pDf?2, complete sequence Epstein-Barr virus, artlfactual joining of B95-8 complete genome and the sequences from l^ji of the large deletion found in B95-8
Human henMsvims 4 strain AG876, complete genome hiuman herpesvirus 4 EBNAl m l ^ A , partial cds Human herpesvirus 4, isolate JF2 nuclear antigen EBNA-1 gene, partial cds, C-tenninal unique domain
1343 111343 1343 ||1343 1343 1304 1149 1074
1343 1304 1149 1074
Tyl#
100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
92%
79%
He sol Pong E nhat 0.0 ||100%
0.0 Jl98%
0.0 |{98%
0.0 ||98%
0.0 ||98%
0.0 ||98%
0.0 0.0 0.0 0.0 0.0 0.0
98%
Noi H I gen
d
98% ]|
98%
97%
96%
98%
Ket qua dio thay, toan bd 765 typ ciia SI hoan toan dong nhat (100%) vdl chuoi EBNA-1 ciia chiing GDI (Quing Dong, Trung Quoc) dang ky trong Ngin hing Gen l i AY961628. I^pt dieu hoan toin die biet la d cho, chiing SI phan lap tif mot benh nhan ngudi mien Nam (thanh pho H6 Chi l*ih). Nhu vay, chiing toi sd bp nhan xet, EBV dong Quing E)6ng ed miit dp giy benh rat cao d vung Nam Trung Quoc, vdi ty l4 tien trien ung thU l i t cao, (^ od mat tai mien Bac Viet Nam.
Trinh tu nucleotide v i amino add doan gen EBNA-leua chiing SI (trong so cac mau benh pham thu tai m&i Nam) duBc trinh bay tai Hinh 1.
3.2. So sanh doi chiSu chuoi gen EBNA- 1 cua hai chung cua Vift Nam vdi mot so chdng cua the gidi
Hai chiing ciia Viet Nam deu cho sin pham EBNA-1 l i 765 bp, ehUng td khong ed bat ky dot
bien them-bdt (in-del mutation) trong vCing gen niy. Sau khi truy cap Ngan hing gen, chiing tdi thu dUdc mpt so chiing the gidi cung cap gen EBNA-lj dd i i chiing GDI (Trung^ Quoc), chiing B95-8 (chiing co dien, co 2 chuoi gen), chiing CIS (Trung Quoc), chiing JF2 (khdng ro xuat xU) va chiing AG876 (Ghana). Ket qua so sanh doi chieu trinh biy d Hinh 2 cho thay, hai chiing EBV (SI va HN2) ciia Viet Nam cd thanh phan nucleotide giong vdi chiing GDI ciia Trung Quoc gan nhU tuyet doi (99%), trong khi dd eac chiing khac tuy cd mile dp dong nhat nucleotide giiis chiing vdl nhau, nhUng khic rat Idn so vdl cac chiing niy ciia Viet Nam va Trung Quoc. Bie biet, chiing CIS (Trung Quoc) cd 9 nucleotide (3 bd ma cho 3 amino acid) them vio d dau 3' ciia EBNA-ltUdng doi khic biet so vdi cic chiing dang so sinh (Hinh 2).
Y HQC VlgT NAM THANQ 6 - S6 1/2011 E B N A - 1 S I
c HcoioorcwioiuiocTUX i*ecco»*TTTO»owic M tac«aft»owr TTMOAGTICTI
Or-rcTToeTOTTCCACAAIOTCOT RTT ACAcr, C ' : T T TGOft*TCCCCCCT0C»CCe
ACIl*CCTOGCCC*eTWW;OC(«:iCC»TtirreT0TTATTTC»TOOK:TTTTI«:**ACTC*t*M TTTSeTMOOTI IT0»»OO»TOCMTt**00K:CT TOTTMMCMWCCC
'TOTCTeCACCTTTaftCCATCaADTfLQI CCTATGaTESUOOCaCTDCCCC StUCXiETaATOItCCaMATCACCG*
CMCMCWGeTMTCGACIkTGACraiTalkCOMGOOCIWSka •
Hinh 1. Trinh bay chuoi nucleotide va amino acid suy dlln doan gen EBNA-1 cua chiing SI. Dong tren la trinh tU nucleotide, ddng dUdi Ici amino acid tUdng irtig vdl c^c bg ma. Dau (*) cuoi cung ]h ky
hl$u bd ma ket thuc gen.
3.3. PhSn b'ch ty* 1$ dBng nhdit ve nucleotide vd amino acid cua gen EBNA-1 giu'a cac chiing EBV Vi$t Nam vh the gidi
Tam chiing EBV ciia the gidi va Viet Nam dang nghien culi (cac chung HN2 va SI) dUdc phan b'ch ty te (%) dong nhat ve nucleotide va tUdng dong ve amino acid. Ket qua dUdc trinh bay d Bang 1. Ket qua cho thay, chiing HN2 va SI CO mu'c dp dong nhat (identity) den 99% ve nucleotide va 99 -100% ve amino acid vdi chiing GDI (Quang Dong) ciia Trung Quoc. Cac chiing ciia the gic^ (chiing 895-8, ca 2 loai; chiing
AG876; Chung C18 va chung JF2) co ty I? dong nhat (nucleotide) va tu'dng dong (amino acW) thap hdn rat nhieu khi so sanh chuoi vdl cac chiing ciia Vl^t Nam. Mifc dp blen dpng thanh phan gen giCta cac chung la khoang 3 -10% (90 - 97% dong nhat) ve nucleotide ding nhU amino acid {Bang 1). NhU vay, ve dSc dian di truyen phan tu* cua cac chiing EBV ciia Vi$t Nam va cac chiing vung Nam Trung Quoc la hoan toan gioig nhau, trong khi do so vdi cac chiing viing khac ciia the gidi la khac nhau.
Bang 1. Ty le (%) dong nhat ve nucleotide (tren dUdng cheo) va amino add (du'd^ dUdng cheo) ua cac Chun
GDI B95- 8(a) B95- 8(b) AG876 CIS JF2 HN2 SI
q EBV Viet GDI
96 96 92 91 95 99 100
^am va the B95- 8(a)
98 ma: .-,• I-
100 92 92 94 95 96
gidi B95- 8(b) 98 100 -j^Si;}^%r
92 92 94 95 96
AG876 97 96 96
t;'.' mi.!
92 96 92 92
C18 96 96 96 96 93 90 91
JF2 98 97 97 98 96 94 95
HN2 99 97 97 96 95 97
•:^^
99 SI 99 97 97 97 95 97 99
-m
102
Y Hpc VIJT NAM THANG 6 - s6 1/2011
QD1-CH-Ay9 , QTSCCCCi
9)1-CH-KIS ; TOOKXAOCI^TCanaTCMMMMiaTICCIACCCIUMkmilXlUUlCATr
Hinli 2. So sanh doi chieu trinh tU nucleotide eiia gen EBNA-1 giiJa cic chiing EBV ciia Viet Nam (Chung HN2 v i SI) vdi mpt so chiing hien co trpng Ngin hing gen (GDI, CIS, B95-8, JF2, AG876).
Ghidiii:DSu (.) bleu hien nucleotide eiia cic chiing giong vdi nucleotide tUdng tU eiia chiing GDI; sai khic nucleotide bleu thj bang chinh chu' cai ky hieu ciia chiing.
EBNA-1 nucleotide (NJ)
100
1
L 1
ii» L JSL.a
«e
»
- J F 2 - 0 2 1 1 9 7
10U " " HN2-VN
I G D 1 - C N - A Y 9 6 1 6 2 8 looi BeS-S-AJ507739 lool B95-a-V015S5
Hinh 3. r>l6i quan he nguon goc phi he giuS cac chiing EBV Viet Nam v i the gidi tren cP sd phan tich dO' lieu gen EBNA-1 ve thanh phan nucleotide v i amino acid, xie lap bang chuong trinh i>1E_GA4.0 (phuPng phap ket noi lien ke NJ, neighbour-joining, sU dung dp tin cay 1000 bootstrap). Chi_s5 tren
cae nhanh bieu hien dp tin ciy ciia phUdng phip; cac chiing eiia the gidi cd kem them so dang ky Ngln hing gen; cac chiing ciia Viet Nam (SI; HN2) dupe boi dam.
Y HQC VlgT NAM THANG 6 - Sti 1/2011 3.4. Phan tich moi quan h$ pha h$ ngu'dn
goc cua EBV difit Mho dO* li$u gen EBNA-1 BSng ChUdng trinh GENEDOC2.5 vh MEGA4.1, chiing toi SLT dyng 612 nucleotide chu5l gen EBNA-1 v4 amino add ciia 8 chiing d l ph3n tich phei h^ vd xdc l§p moi quan h | giOa cSc chiing. KSt qud trinh bdy d Hinh 3.
Ph3n tich phd h? d i ^ tr^n dff ll^u gen EBNA-1, cho thSiy: Ch ve nucleotide vd amino acid, cdy phd h§ dSu Cho ket qud thSng nhSt: Cdc chiing EBV cua Vi§t Nam thu$c phSn nhdm cCing chiing GDI (AY961628), 1^
chiing dpc lyt cao phSn l$p vCing Nam Trung QuSc vd g3n vdi chiing c6 dl§n 895-8 (A3507799 vd VOISSS).
Cdc chiing khdc ciia th§ gidi Id C18 (AY825078), AG876 (DQ279927) va JF2 (U21197), l$p thSnh mOt nhdm khdc, khdc v6\ cdc chiing nguBn g6c Nam Trung Qu6c vd Vi?t Nam (Hinh 3).
NhU v§y, phan tfch phd h§ dM<i vao chu5i gen EBNA-1, cd ve dO' li^u nucleotide vd amino acid, dd cho thSiy cdc chiing EBV cua Vi?t Nam dUcjfc phdn vdo ciing nhom vdi chung phdn l|p tai Qudng Dong (Trung Q u ^ ) , chiiTig minh k ^ qua nguon goc phd h$ cua cdc chung ndy cd the tCr Trung Quoc xam nhdp vdo Vi|t Nam. Hay ndi each khac, v?t djch te EBV keo tCi* Nam Trung Quoc xuyen suot Vi?t Nam vdi ddc trUng ciia sy"
nSi trpi cdc chiing giong vdl GDI ciia Trung Quoc.
V. KET LUAN
Trinh b/ nucleotide vd amino add cac chuoi gen EBNA-1 ciia hai chiing SI va HN2 ciia Viet Nam dd duoc xac dinh va phan b'ch cho thay, chung c6 d$c diem thanh phan gen vd quan he phd h^ gi5ng vdi diiing GDI, dong Quang Dong. Dong EBV Quang Dong gay ung tJiU NPC rat cao, dieu dd canh bdo nguy cd ndy tai Viet Nam khi phdt hi^n cdc chiing gidng GDI tai cdc ndi khdc trong cd nude.
Ldi cam dit: dm dn tdi trd kinh phi nhdnh KClO.31.01/06-10 (PGS. TS Li Thanh Hda chu nhi?m)
cua de tdi nhd nude KClO.31/06-10 (PGS.TS. Nguyen Dinh Phdc chd nhl$m) di'thi/c hi$n cdng tnnh ndy TAI LI|U THAM KHAO
1. All AK, Salto S, Shibata S, Takada K, Kanda T (2009). Distinctive effects of the Epstein-Ban- virus family of repeats on viral latent gene promoter activity and B-iymphocyte transformation. J !///)?/83(18): 9163-74.
2. Cheng W M , Chan KH, Chen HL, Luo RX, Ng SP, Luk W, Zheng BJ, Ji MF, Liang JS, Sham JS, Wang DK, Zong YS and Ng MH (2002).
Assessing the risk of nasopharyngeal carcinoma on the basis of EBV antibody spectrum. Int J Cancer 97(4): 489-492.
3. Chou J, Lln YC, Kim J, You L, Xu Z, He B, Jablons DM (2008). Nasopharyngeal carcinoma- Review of the molecular mechanisms of tumorigenesis. Head Neck 2Q{7y. 946-63.
4. Cohen J I (2006). Vinatogy and molecular biology of Epstein-Barr virus. In "^Epste/n-Ban- Vinjf pp 21- 37. Edited by Tsdis A and Jenson HB.Taytor and Frands Group LLC, New York NY.
5 Do NV, Ingemar E, Phi PT, Jenny A, Chinh TT, Zeng Y and Hu L (2008). A major EBNAl variant from Asian EBV isolates shows enhanced transcriptional activity compared to prototype 895.8. Wn;j^e5l32(l-2):15-24.
6. L£ Thanh H6a, Vu Thj T1§n, Ho&ng Thi Minh Chau, Le Thanh Hh, Nguyin Dinh Phiic (2010). Xac djnh 3 phan typP-ala, P-thr va V-val ciia EBNA-1 d EBV phan lap tai Vi?t Nam. Tap dii Nghlin cuU YhqcTOiS): 8-12.
7. Murray PG and Young IS. (2001). Epstein^air vims Infirbon: basis of malgnancy and patently for therapy. ExpeitRevMolMed, 3(28): 1-20.