Reverse genetics modification of cytomegalovirus antigenicity and immunogenicity by CD8 T-cell epitope deletion and insertion.
The advent of cloning herpesviral genomes as bacterial artificial chromosomes (BACs) has made herpesviruses accessible to bacterial genetics and has thus revolutionised their mutagenesis. This opened all possibilities of reverse genetics to ask scientific questions by introducing precisely accurate mutations into the viral genome for testing their influence on the phenotype under study or to create phenotypes of interest. Here, we report on our experience with using BAC technology for a designed modulation of viral antigenicity and immunogenicity with focus on the CD8 T-cell response. One approach is replacing an intrinsic antigenic peptide in a viral carrier protein with a foreign antigenic sequence, a strategy that we have termed "orthotopic peptide swap". Another approach is the functional deletion of an antigenic peptide by point mutation of its C-terminal MHC class-I anchor residue. We discuss the concepts and summarize recently published major scientific results obtained with immunological mutants of murine cytomegalovirus.
Institute for Virology, University Medical Center of the Johannes Gutenberg-University Mainz, Hochhaus am Augustusplatz, 55101 Mainz, Germany. lemmermann@uni-mainz.de
Niels A W
NA
Lemmermann
Kai A
KA
Kropp
Christof K
CK
Seckert
Natascha K A
NK
Grzimek
Matthias J
MJ
Reddehase
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics*; D006801:Humans; D016254:Mutagenesis, Insertional / Q000379:methods*; D017384:Sequence Deletion / Q000235:genetics*
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte
Annu Rev Immunol. 1999;17:51-88
10358753
J Virol. 1999 Aug;73(8):7056-60
10400809
Nature. 1989 Feb 16;337(6208):651-3
2465495
Science. 1989 Jun 16;244(4910):1307-12
2660262
J Virol. 2000 Aug;74(15):6964-74
10888635
Science. 2010 Apr 2;328(5974):102-6
20360110
Lancet. 2003 Oct 25;362(9393):1375-7
14585640
Med Microbiol Immunol. 2008 Jun;197(2):65-73
18087722
Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8794-7
1528894
Hum Gene Ther. 1998 Dec 10;9(18):2787-94
9874276
Immunity. 2004 Aug;21(2):149-53
15308096
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14223-8
14623981
J Immunol. 2007 Sep 1;179(5):3203-13
17709536
Med Microbiol Immunol. 2008 Jun;197(2):109-15
18193454
Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):104-8
7678330
J Immunol. 2006 Jul 1;177(1):450-8
16785542
Nature. 1984 Nov 22-28;312(5992):369-71
6095095
Immunogenetics. 2005 Apr;57(1-2):33-41
15744535
Annu Rev Microbiol. 1987;41:543-71
2825588
Biotechniques. 2006 Feb;40(2):191-7
16526409
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12396-401
14519856
Appl Bioinformatics. 2003;2(3):155-8
15130801
J Virol. 2004 Mar;78(5):2255-64
14963122
Antiviral Res. 2007 Nov;76(2):104-10
17658624
Curr Top Microbiol Immunol. 1990;163:153-84
2242679
Immunol Cell Biol. 2006 Dec;84(6):543-50
16956387
Med Microbiol Immunol. 2008 Jun;197(2):125-34
18343947
Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14759-63
9405686
Immunity. 1997 Jan;6(1):57-66
9052837
J Virol. 1999 Oct;73(10):8320-9
10482582
Curr Protoc Immunol. 2007 May;Chapter 10:Unit 10.32
18432982
J Virol. 1988 Mar;62(3):1061-5
2828654
J Virol. 2001 Mar;75(6):2692-705
11222693
Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8245-50
9653172
J Immunol. 2001 Aug 1;167(3):1515-21
11466372
J Gen Virol. 2004 May;85(Pt 5):1301-1312
15105547
EMBO J. 1999 Feb 15;18(4):1081-91
10022849
J Gen Virol. 2010 Jun;91(Pt 6):1524-34
20147515
J Bacteriol. 1997 Jul;179(13):4426-8
9209066
Nat Immunol. 2002 Jun;3(6):529-35
12021778
Viral Immunol. 2009 Apr;22(2):91-103
19326996
J Infect Dis. 2001 Jul 15;184(2):192-5
11424017
Med Microbiol Immunol. 2008 Jun;197(2):135-44
18340461
J Exp Med. 2002 Sep 16;196(6):805-16
12235213
J Virol. 2000 Feb;74(4):1871-84
10644360
J Exp Med. 2005 Aug 1;202(3):379-86
16061727
Curr Top Microbiol Immunol. 2008;325:315-31
18637514
Immunity. 1997 Jun;6(6):715-26
9208844
Methods Mol Biol. 2004;256:269-79
15024172
J Virol. 2002 Mar;76(5):2316-28
11836410
J Virol. 1999 Oct;73(10):8612-22
10482614
J Immunol. 1997 Feb 15;158(4):1507-15
9029084
J Exp Med. 1998 Sep 21;188(6):1047-54
9743523
J Virol. 2010 Feb;84(3):1221-36
19906905
Proc Soc Exp Biol Med. 1956 Jun;92(2):424-30
13350368
J Virol. 2006 Aug;80(15):7613-24
16840340
Genomics. 2001 Apr 1;73(1):56-65
11352566
Traffic. 2009 Dec;10(12):1745-52
19761542
J Virol. 2006 Jul;80(14):6873-82
16809293
J Exp Med. 2005 Sep 5;202(5):673-85
16147978
Nucleic Acids Res. 1999 Mar 15;27(6):1555-7
10037821
J Gen Virol. 2003 Jan;84(Pt 1):17-28
12533697
J Gen Virol. 2009 Oct;90(Pt 10):2395-2401
19553390
Immunogenetics. 1999 Nov;50(3-4):213-9
10602881
J Virol. 2006 Nov;80(21):10436-56
16928768
J Exp Med. 1993 May 1;177(5):1469-73
8478616
J Virol. 1985 Aug;55(2):264-73
2991554
Lancet. 2003 Oct 25;362(9393):1343-4
14585632
J Exp Med. 1987 Mar 1;165(3):650-6
3029272
Nucleic Acids Res. 2005 Feb 24;33(4):e36
15731329
J Gen Virol. 1996 Oct;77 ( Pt 10):2615-23
8887498
J Virol. 2005 Mar;79(6):3615-26
15731256
Microbes Infect. 2003 Nov;5(13):1263-77
14623023
Proteins. 1992 May;13(1):70-85
1594579
Annu Rev Immunol. 1999;17:739-79
10358773
J Virol. 2001 Jul;75(14):6584-600
11413326
Nature. 1991 May 23;351(6324):290-6
1709722
Nat Immunol. 2002 Nov;3(11):1019-25
12407410
Cancer Res. 1995 Apr 15;55(8):1741-7
7536130
Nature. 1987 Oct 8-14;329(6139):512-8
2443855
J Exp Med. 2003 May 19;197(10):1245-53
12756263
Nat Immunol. 2005 Apr;6(4):382-9
15735650
Virus Res. 2011 May;157(2):161-74
20933556
Nat Genet. 1998 Oct;20(2):123-8
9771703
J Virol. 1998 Mar;72(3):1797-804
9499030
Immunogenetics. 1995;41(4):178-228
7890324
J Virol. 2002 Jan;76(1):151-64
11739681
N Engl J Med. 1995 Oct 19;333(16):1038-44
7675046
Eur J Immunol. 1991 Jul;21(7):1697-701
2060579
J Virol. 2008 Jun;82(12):5781-96
18367531
Nat Rev Immunol. 2002 Nov;2(11):831-44
12415307
J Virol. 1996 Mar;70(3):2044-8
8627734
Pharmacol Ther. 2003 Jun;98(3):269-97
12782241
J Virol. 1996 Dec;70(12):8833-49
8971012
J Virol. 2000 Dec;74(24):11495-503
11090146
Science. 1992 Jul 10;257(5067):238-41
1352912
J Immunol. 2006 Sep 1;177(5):2917-25
16920927
J Virol. 2007 Feb;81(3):1241-50
17108043
Immunol Rev. 1999 Dec;172:97-108
10631940
Cell Host Microbe. 2010 Sep 16;8(3):284-91
20833379
J Virol. 1987 Oct;61(10):3102-8
3041033
Proc Natl Acad Sci U S A. 1987 Oct;84(20):7213-7
2823255
Curr Top Microbiol Immunol. 2008;325:397-415
18637518
J Virol. 2008 Oct;82(20):9900-16
18684825
Gene. 1982 Apr;18(1):39-46
6286417
Cell. 1986 Mar 28;44(6):959-68
2420472
Gene. 1993 Aug 25;130(2):167-73
8395449
Biochemistry. 2010 Mar 23;49(11):2443-53
20166740
J Immunol. 2006 Mar 15;176(6):3760-6
16517745