Epstein-Barr virus: more than 50 years old and still providing surprises.
It is more than 50 years since the Epstein-Barr virus (EBV), the first human tumour virus, was discovered. EBV has subsequently been found to be associated with a diverse range of tumours of both lymphoid and epithelial origin. Progress in the molecular analysis of EBV has revealed fundamental mechanisms of more general relevance to the oncogenic process. This Timeline article highlights key milestones in the 50-year history of EBV and discusses how this virus provides a paradigm for exploiting insights at the molecular level in the diagnosis, treatment and prevention of cancer.
Warwick Medical School, The University of Warwick, Coventry CV4 7AL, UK.
Lawrence S
LS
Young
Department of Oral and Craniofacial Sciences and Oral Cancer Research Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
Lee Fah
LF
Yap
Institute of Cancer and Genomic Medicine, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK.
Paul G
PG
Murray
D020031:Epstein-Barr Virus Infections / Q000821:virology; D004854:Herpesvirus 4, Human / Q000502:physiology*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008223:Lymphoma / Q000821:virology; D009375:Neoplasms, Glandular and Epithelial / Q000821:virology
Clin Cancer Res. 2007 Sep 1;13(17):5124-32
17785567
Lancet Oncol. 2012 Jun;13(6):607-15
22575588
J Virol. 1998 May;72(5):4371-8
9557727
J Virol. 1994 Sep;68(9):6069-73
8057484
N Engl J Med. 2004 Mar 25;350(13):1328-37
15044644
Int J Cancer. 1977 Nov 15;20(5):663-72
200569
Immunity. 1998 Sep;9(3):405-11
9768760
Oncogene. 2014 Mar 6;33(10):1258-64
23503461
J Virol. 1979 Oct;32(1):8-18
232190
Int J Cancer. 1978 Dec;22(6):662-8
214405
Lancet. 1973 May 26;1(7813):1153-5
4123541
Int J Cancer. 2001 Sep;93(6):810-6
11519042
Int J Cancer. 2006 Apr 15;118(8):1853-61
16385563
Genome Biol Evol. 2014 Apr;6(4):846-60
24682154
PLoS Pathog. 2015 Jun 12;11(6):e1004979
26070070
Oncogene. 1996 Dec 19;13(12):2541-9
9000128
PLoS Pathog. 2009 Jan;5(1):e1000255
19119421
J Virol. 2007 Jul;81(14 ):7363-70
17494074
Br Med J. 1968 Dec 21;4(5633):746-8
4881420
J Pathol. 2011 Mar;223(4):496-510
21294123
Int J Cancer. 1974 Jun 15;13(6):755-63
4136722
N Engl J Med. 1985 Dec 19;313(25):1564-71
2999595
Cell Res. 2015 Jul;25(7):785-800
25916549
N Engl J Med. 1970 Oct 22;283(17):934-5
4917728
Cell Rep. 2013 Dec 12;5(5):1204-13
24316071
J Virol. 2004 Dec;78(23):13253-61
15542676
Semin Cancer Biol. 2012 Apr;22(2):162-5
22210180
PLoS Pathog. 2014 Feb 27;10(2):e1003974
24586173
J Gen Virol. 1992 Jun;73 ( Pt 6):1547-51
1318948
PLoS Pathog. 2009 Jul;5(7):e1000530
19649319
Int J Cancer. 1976 Jan 15;17(1):47-56
946170
J Virol. 2010 Mar;84(6):2893-901
20042495
Cancer Res. 2012 Mar 1;72(5):1116-25
22282657
J Bacteriol. 1966 Mar;91(3):1248-56
4160230
EMBO J. 1989 Oct;8(10):2897-903
2555151
Nature. 1972 May 5;237(5349):33-4
4113130
Cancer Res. 1999 Nov 1;59(21):5452-5
10554016
Nat Med. 1996 May;2(5):551-5
8616714
J Infect Dis. 2009 Jan 1;199(1):31-8
19032105
J Virol. 1987 May;61(5):1310-7
3033261
Cancer Res. 1974 May;34(5):1172-8
4842360
Immunity. 1998 Sep;9(3):395-404
9768759
Lancet. 2005 Jun 25-Jul 1;365(9478):2216-24
15978930
Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9150-4
8415670
Semin Cancer Biol. 2012 Apr;22(2):166-72
22178394
Int J Cancer. 2015 Feb 15;136(4):E127-35
25196065
Nature. 1984 Nov 29-Dec 5;312(5993):449-50
6095104
Blood. 1983 Jun;61(6):1265-8
6839024
Proc Natl Acad Sci U S A. 1985 Jun;82(12):4085-9
2987963
J Infect Dis. 2007 Mar 15;195(6):799-808
17299709
J Neurol Sci. 2016 Feb 15;361:213-9
26810546
J Exp Med. 1993 Feb 1;177(2):339-49
8381153
EMBO J. 1996 Jun 17;15(12):3117-26
8670812
J Virol. 2007 Dec;81(24):13566-77
17898050
J Virol. 1990 Sep;64(9):4084-92
2166806
Blood. 2005 Dec 15;106(13):4249-52
16123211
Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4730-5
12665622
Virology. 1996 Jun 15;220(2):367-76
8661388
J Natl Cancer Inst. 1967 Nov;39(5):933-45
6066443
J Virol. 2013 Jan;87(2):1172-82
23152513
Cell. 1992 Apr 3;69(1):119-28
1555236
J Gen Virol. 1988 May;69 ( Pt 5):1051-65
2836550
J Virol. 1992 May;66(5):3257-62
1313931
Transplant Proc. 1969 Mar;1(1):106-12
4944206
Int J Cancer. 2013 Jul;133(1):79-87
23280823
J Virol. 1992 Jan;66(1):122-31
1309242
J Clin Invest. 2012 Apr;122(4):1487-502
22406538
Int J Cancer. 1985 Nov 15;36(5):545-7
4055129
Semin Cancer Biol. 2012 Apr;22(2):117-26
22311401
Clin Cancer Res. 2004 Mar 1;10(5):1698-705
15014022
Nat Med. 2002 Oct;8(10):1098-104
12219084
Br J Cancer. 2000 Jun;82(12):1946-51
10864202
Cell. 1985 Dec;43(3 Pt 2):831-40
3000618
J Virol. 1982 Dec;44(3):834-44
6294333
Science. 1967 Sep 1;157(3792):1064-5
6036237
EMBO J. 1987 Sep;6(9):2743-51
2824192
J Virol. 2010 Jan;84(2):1158-68
19889783
Nucleic Acids Res. 2014 Jan;42(Database issue):D68-73
24275495
Clin Cancer Res. 1998 Mar;4(3):665-9
9533535
Proc Natl Acad Sci U S A. 1966 Dec;56(6):1699-704
16591407
EMBO J. 1996 Jan 15;15(2):375-82
8617212
Int J Cancer. 1996 Nov 4;68(3):285-90
8903467
PLoS Pathog. 2015 Jan 15;11(1):e1004561
25590614
Hum Pathol. 2000 Jan;31(1):45-50
10665912
J Virol. 2014 Sep;88(18):10662-72
24991008
Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):E3473-82
23161911
Nat New Biol. 1973 Aug 22;244(138):245-7
4353684
Proc Natl Acad Sci U S A. 1984 Dec;81(23):7632-6
6209719
Br J Cancer. 2003 May 19;88(10):1566-9
12771923
N Engl J Med. 1988 Mar 24;318(12):733-41
2831453
Curr Top Microbiol Immunol. 2015;391:385-405
26428382
J Pathol. 1992 Jan;166(1):1-5
1311374
Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2313-8
19139406
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14269-74
14603034
Cell Rep. 2013 Oct 31;5(2):458-70
24120866
Virology. 2006 Jun 20;350(1):164-70
16490228
J Bacteriol. 1966 Jul;92(1):275-6
5328753
J Virol. 1999 Dec;73(12):9827-31
10559294
Cell. 1995 Feb 10;80(3):389-99
7859281
J Virol. 1992 May;66(5):2689-97
1313894
Nature. 1978 Aug 24;274(5673):756-61
210392
Clin Exp Immunol. 1969 Nov;5(5):443-59
4902604
Blood. 1998 Oct 1 ;92 (7):2477-83
9746788
Nature. 1985 Feb 28-Mar 6;313(6005):812-5
2983224
Virology. 2015 Jan 1;474:117-30
25463610
Proc Natl Acad Sci U S A. 1968 Jan;59(1):94-101
5242134
BMC Genomics. 2013 Nov 19;14:804
24252203
Int J Cancer. 2006 Apr 1;118(7):1736-42
16217758
Nat Rev Cancer. 2004 Oct;4(10):757-68
15510157
Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6400-5
20308568
J Virol. 1998 Nov;72(11):8559-67
9765394
Semin Cancer Biol. 2012 Apr;22(2):144-53
22249143
J Virol. 1988 Jun;62(6):1862-9
2835494
J Virol. 2015 Feb;89(4):2301-12
25505080
Science. 2004 Apr 30;304(5671):734-6
15118162
Cancer Res. 1981 Nov;41(11 Pt 1):4237-42
6272968
J Pathol. 2015 Jan;235(2):323-33
25251730
Clin Cancer Res. 2014 Oct 1;20(19):5009-22
25124688
Cancer Res. 1994 Apr 1;54(7):1843-8
8137299
Nature. 1967 Nov 25;216(5117):810-1
6074953
Am J Pathol. 1987 Oct;129(1):86-91
2821817
J Virol. 1993 Apr;67(4):2014-25
8445720
Nature. 2014 Sep 11;513(7517):202-9
25079317
Nature. 1988 Feb 25;331(6158):719-21
2830541
J Virol. 1977 Sep;23(3):503-8
197258
J Natl Cancer Inst. 1970 Jan;44(1):225-31
11515035
Am J Pathol. 1992 Apr;140(4):769-74
1314023
Cancer Res. 2007 Mar 1;67(5):2382-8
17332371
Am J Clin Pathol. 1985 Sep;84(3):385-90
2994459
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10962-6
7971992
J Virol. 2005 Aug;79(16):10709-17
16051863
Adv Hematol. 2012;2012:149780
22593768
N Engl J Med. 1976 Jun 17;294(25):1355-9
177872
Chin J Cancer. 2014 Dec;33(12):604-8
25322866
Lancet. 1984 Mar 17;1(8377):583-7
6142304
N Engl J Med. 1974 Nov 28;291(22):1145-8
4138509
J Virol. 2005 Jun;79(12):7355-62
15919890
Lancet. 1990 Jan 20;335(8682):128-30
1967431
J Clin Pathol. 2004 May;57(5):487-91
15113855
J Virol. 1996 Aug;70(8):5131-42
8764021
J Clin Oncol. 2014 Mar 10;32(8):798-808
24344220
Nature. 1978 Mar 23;272(5651):373-5
204874
Nature. 2007 May 17;447(7142):326-9
17507983
Gastroenterology. 2009 Sep;137(3):824-33
19445939
Lancet. 1995 Jan 7;345(8941):9-13
7799740
Nat Genet. 2014 Jun;46(6):573-82
24816253
J Virol. 2009 Apr;83(8):3968-76
19193789
Infect Agent Cancer. 2014 Nov 17;9(1):38
25473414
J Virol. 2005 Nov;79(22):13993-4003
16254335
Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3366-71
17360652
Int J Cancer. 1983 Jun 15;31(6):727-32
6305850
Surgery. 1981 Aug;90(2):204-13
6266059
Mol Ther. 2003 Dec;8(6):964-73
14664799
Nucleic Acids Res. 2010 Apr;38(6):1932-49
20034954
Int J Cancer. 1971 Sep 15;8(2):192-201
5133848
Virology. 1987 Sep;160(1):151-61
2820125
Semin Cancer Biol. 2002 Dec;12(6):451-62
12450731
Transplantation. 2002 Oct 27;74(8):1095-102
12438953
PLoS Pathog. 2011 May;7(5):e1001338
21573183
Lancet. 1980 Jun 21;1(8182):1355-6
6104142
Lancet. 1980 Mar 8;1(8167):536-7
6102249
Oncogene. 1993 Dec;8(12):3385-91
8247541
Clin Invest Med. 2014 Oct 04;37(5):E320-30
25282138
Am J Pathol. 2002 Oct;161(4):1207-13
12368194
Curr Treat Options Oncol. 2013 Jun;14(2):224-36
23549980
J Virol. 1990 May;64(5):2319-26
2157888
Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8479-83
8397406
J Clin Oncol. 2002 Oct 15;20(20):4255-60
12377970
Nat Genet. 1998 Oct;20(2):129-35
9771704
Blood. 1982 Jul;60(1):180-7
6282364
Blood. 2009 Apr 23;113(17):3931-7
19029440
J Virol. 2015 May;89(10):5222-37
25787276
Pediatr Res. 1995 Oct;38(4):471-8
8559596
Oncogene. 2008 Jan 17;27(4):421-33
17653091
PLoS One. 2012;7(6):e39217
22768064
Mod Pathol. 2014 Jan;27 Suppl 1:S17-29
24384850
Curr Biol. 1993 Jun 1;3(6):333-9
15335726
J Virol. 1988 Mar;62(3):902-11
2828685
PLoS One. 2012;7(5):e36939
22590638
Trends Immunol. 2008 Apr;29(4):195-201
18328785
Int J Cancer. 1979 May 15;23(5):610-7
222690
J Virol. 2016 Apr 14;90(9):4383-93
26889033
J Virol. 1992 Aug;66(8):5030-9
1321285
J Virol. 2015 May;89(10):5581-91
25740983
Am J Surg Pathol. 2010 Mar;34(3):405-17
20154586
Nat Rev Microbiol. 2008 Dec;6(12):913-24
19008891
EMBO J. 1997 Oct 15;16(20):6131-40
9359753
Cancer. 2012 Feb 1;118(3):698-710
21720996
J Natl Cancer Inst. 1969 Nov;43(5):1147-57
5353242
Antiviral Res. 2014 Apr;104:73-83
24486954
J Virol. 2005 Jan;79(2):1296-307
15613356
Int J Cancer. 1990 Nov 15;46(5):801-4
2172169
Nature. 1984 Jul 19-25;310(5974):207-11
6087149
Lancet. 1991 Feb 9;337(8737):320-2
1671232
Pediatr Transplant. 2009 Jun;13(4):393-6
19032417
Nature. 1970 Dec 12;228(5276):1056-8
4320657
Br Med J. 1974 May 4;2(5913):253-6
4406463
J Virol. 2011 Nov;85(21):11291-9
21880770
J Virol. 2015 Mar;89(5):2684-97
25520514
Int J Cancer. 2007 Jan 1;120(1):60-6
17058198
J Virol. 1998 Jul;72(7):6034-9
9621066
J Gastroenterol Hepatol. 2009 Mar;24(3):354-65
19335785
Ann Surg. 1983 Sep;198(3):356-69
6311121
Nature. 1985 Feb 14-20;313(6003):597-600
3881681
Clin Cancer Res. 2012 Sep 15;18(18):5061-70
22761471
Blood. 2005 Dec 15;106(13):4339-44
16076866
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13765-70
9811875
J Virol. 2007 Jan;81(2):1037-42
17079287
C R Seances Acad Sci D. 1980 Sep 15;291(2):237-9
6775833
Blood. 2005 Dec 15;106(13):4345-50
16131568
Lancet. 1982 Sep 18;2(8299):631-3
6125777
Virology. 1986 Oct 15;154(1):56-66
3019008
Int J Cancer. 2015 Mar 15;136(6):1371-80
25099163
Lancet. 1964 Mar 28;1(7335):702-3
14107961
J Virol. 2011 Jan;85(1):165-77
20980506
Proc Natl Acad Sci U S A. 1984 Aug;81(15):4652-6
6205400
J Exp Med. 2007 Aug 6;204(8):1863-73
17620360
Cancer Res. 1966 Jun;26(6):1189-201
5329907
J Virol. 2011 Dec;85(23):12102-13
21849433
Nature. 1988 Jun 2;333(6172):455-7
2836734
Nat Genet. 2014 Aug;46(8):866-71
24952746
J Virol. 2012 Aug;86(15):7976-87
22623780
Ann Oncol. 1994;5 Suppl 1:113-6
8172807
Nat Rev Immunol. 2001 Oct;1(1):75-82
11905817
J Virol. 2011 Oct;85(19):9801-10
21752900
J Exp Med. 1990 Jan 1;171(1):345-9
1688611
Immunity. 2000 Oct;13(4):485-95
11070167
J Pathol. 1991 Sep;165(1):17-24
1659626
Int J Cancer. 2015 Mar 1;136(5):E301-12
25213622
J Gen Virol. 2003 Jun;84(Pt 6):1443-50
12771413
J Virol. 2009 Aug;83(15):7749-60
19439479
Cell. 2015 Aug 27;162(5):1090-100
26279189
Virology. 1977 Jan;76(1):152-63
189490
Oncogene. 2003 Aug 11;22(33):5108-21
12910248
Curr Opin Infect Dis. 2011 Oct;24(5):435-41
21885920
Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16544-9
25313069
Blood. 2010 Oct 28;116(17 ):3249-57
20644117
N Engl J Med. 1995 Sep 14;333(11):693-8
7637746
Proc Natl Acad Sci U S A. 1983 Feb;80(3):820-4
6402776
J Comput Aided Mol Des. 2016 Apr;30(4):285-303
27048620
Blood. 2006 Dec 1;108(12):3786-91
16917006
Hum Pathol. 1997 May;28(5):556-62
9158704
Lancet. 1982 May 1;1(8279):1026-7
6122840
Lancet. 1975 Apr 26;1(7913):935-40
48119
Cancer. 1997 Aug 1;80(3):357-63
9241068
J Virol. 1979 Dec;32(3):710-6
229261
Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9131-5
8090780
Immunol Rev. 2013 Jul;254(1):207-24
23772622
Immunity. 2000 Oct;13(4):497-506
11070168
Nat Commun. 2015 Jul 02;6:7353
26135619
Semin Cancer Biol. 2012 Apr;22(2):79-86
22245473
Nature. 1998 Oct 1 ;395(6701):462-9
9774102
J Virol. 2005 Dec;79(24):15323-30
16306603
Int J Cancer. 1988 Sep 15;42(3):329-38
2843473
N Engl J Med. 1989 Feb 23;320(8):502-6
2536894
J Infect Dis. 2007 Dec 15;196(12):1749-53
18190254
Cancer Res. 2013 Mar 15;73(6):1676-88
23348421
Int J Cancer. 1985 Mar 15;35(3):359-66
2982749
J Med Virol. 2005 May;76(1):82-8
15778977
Nature. 1984 Aug 23-29;310(5979):655-60
6088986
Int J Cancer. 1968 Nov 15;3(6):857-66
4894385
Mol Cell Biol. 1999 Mar;19(3):1651-60
10022853
PLoS Pathog. 2014 May 29;10(5):e1004170
24874410
J Virol. 2010 Dec;84(24):13053-8
20943983
PLoS Pathog. 2009 Mar;5(3):e1000341
19283066
Nat Genet. 2004 Oct;36(10):1099-104
15361873