title: Constitutive and Inducible Innate Responses in Cells Infected by HSV-1-Derived Amplicon Vectors.
abstract: Amplicons are helper-dependent herpes simplex virus type 1 (HSV-1)-based vectors that can deliver very large foreign DNA sequences and, as such, are good candidates both for gene delivery and vaccine development. However, many studies have shown that innate constitutive or induced cellular responses, elicited or activated by the entry of HSV-1 particles, can play a significant role in the control of transgenic expression and in the induction of inflammatory responses. Moreover, transgene expression from helper-free amplicon stocks is often weak and transient, depending on the particular type of infected cells, suggesting that cellular responses could be also responsible for the silencing of amplicon-mediated transgene expression. This review summarizes the current experimental evidence underlying these latter concepts, focusing on the impact on transgene expression of very-early interactions between amplicon particles and the infected cells, and speculates on possible ways to counteract the cellular protective mechanisms, thus allowing stable transgene expression without enhancement of vector toxicity.
authors.affiliation: Université de Lyon, Lyon, F-69003, France; CNRS, UMR5534, Centre de Génétique Moléculaire et Cellulaire, Villeurbanne, F-69622, France.
authors.forename: Eliza
authors.initials: E
authors.lastname: Tsitoura
authors.forename: Alberto L
authors.initials: AL
authors.lastname: Epstein
references.citation: J Virol. 1989 Nov;63(11):4479-88
references.pmid: 2552134
references.citation: Bioessays. 2000 Aug;22(8):761-70
references.pmid: 10918307
references.citation: J Gen Virol. 2006 May;87(Pt 5):1099-1108
references.pmid: 16603509
references.citation: Immunobiology. 2007;212(9-10):877-86
references.pmid: 18086386
references.citation: Mol Ther. 2009 Apr;17(4):707-15
references.pmid: 19223864
references.citation: J Gene Med. 2005 Sep;7(9):1187-99
references.pmid: 15852412
references.citation: J Virol. 1996 Oct;70(10):7190-7
references.pmid: 8794366
references.citation: J Virol. 2006 Apr;80(7):3293-300
references.pmid: 16537596
references.citation: Virol J. 2008 Nov 21;5:140
references.pmid: 19025601
references.citation: J Gene Med. 2008 Feb;10(2):152-64
references.pmid: 18058952
references.citation: Blood. 2009 Apr 2;113(14):3264-75
references.pmid: 18952891
references.citation: Oncogene. 1999 Jan 28;18(4):935-41
references.pmid: 10023669
references.citation: Hum Gene Ther. 1998 Dec 10;9(18):2787-94
references.pmid: 9874276
references.citation: J Virol. 2000 Dec;74(24):11782-91
references.pmid: 11090178
references.citation: J Virol. 2004 Feb;78(4):1675-84
references.pmid: 14747533
references.citation: Expert Opin Biol Ther. 2007 Jul;7(7):975-95
references.pmid: 17665988
references.citation: Virology. 2005 Jun 5;336(2):274-90
references.pmid: 15892968
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10410-5
references.pmid: 11517326
references.citation: Virology. 2001 Nov 10;290(1):115-20
references.pmid: 11882996
references.citation: J Gen Virol. 2003 Jan;84(Pt 1):1-15
references.pmid: 12533696
references.citation: J Virol. 2002 Feb;76(4):1995-8
references.pmid: 11799195
references.citation: J Virol. 2002 Jan;76(2):743-54
references.pmid: 11752164
references.citation: J Virol. 1991 Dec;65(12):7046-50
references.pmid: 1658396
references.citation: J Virol. 1996 Sep;70(9):6358-69
references.pmid: 8709264
references.citation: J Virol. 2008 Mar;82(6):2661-72
references.pmid: 18160441
references.citation: J Virol. 2004 Feb;78(4):1763-74
references.pmid: 14747541
references.citation: Virol J. 2006 Jun 09;3:44
references.pmid: 16764725
references.citation: J Virol. 2008 May;82(10):4688-96
references.pmid: 18321964
references.citation: J Virol. 2001 Oct;75(19):8977-86
references.pmid: 11533161
references.citation: Science. 1994 Nov 25;266(5189):1399-403
references.pmid: 7669103
references.citation: Virology. 2004 Feb 20;319(2):212-24
references.pmid: 14980482
references.citation: J Biol Chem. 2009 Jan 9;284(2):1097-105
references.pmid: 19010780
references.citation: Science. 2000 Feb 25;287(5457):1500-3
references.pmid: 10688801
references.citation: J Immunol. 2001 Oct 1;167(7):3928-35
references.pmid: 11564811
references.citation: J Immunol. 1997 Feb 15;158(4):1763-71
references.pmid: 9029114
references.citation: Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9583-7
references.pmid: 8790373
references.citation: J Biol Chem. 2003 Sep 19;278(38):36059-67
references.pmid: 12844494
references.citation: Gene Ther. 2003 Aug;10(17):1437-45
references.pmid: 12900758
references.citation: J Virol. 2004 Dec;78(24):13582-90
references.pmid: 15564469
references.citation: J Virol. 2004 Sep;78(18):10193-6
references.pmid: 15331752
references.citation: Nat Biotechnol. 2001 Nov;19(11):1067-70
references.pmid: 11689853
references.citation: J Virol. 2002 Mar;76(5):2180-91
references.pmid: 11836395
references.citation: J Virol. 1999 Apr;73(4):2803-13
references.pmid: 10074128
references.citation: Cell Host Microbe. 2007 Mar 15;1(1):23-35
references.pmid: 18005679
references.citation: EMBO Rep. 2006 Sep;7(9):911-8
references.pmid: 16906131
references.citation: J Virol. 2007 Apr;81(7):3455-64
references.pmid: 17229694
references.citation: Cell. 1982 Aug;30(1):295-304
references.pmid: 6290080
references.citation: Mol Ther. 2001 Apr;3(4):591-601
references.pmid: 11319922
references.citation: Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):843-8
references.pmid: 9023344
references.citation: Cell. 1994 May 20;77(4):525-35
references.pmid: 8187174
references.citation: Mol Ther. 2003 May;7(5 Pt 1):604-12
references.pmid: 12718903
references.citation: Gene Ther. 1998 Nov;5(11):1517-30
references.pmid: 9930305
references.citation: Blood. 2001 Jul 15;98(2):287-95
references.pmid: 11435295
references.citation: J Virol. 2003 Jun;77(12):7101-5
references.pmid: 12768029
references.citation: Mol Ther. 2007 Feb;15(2):248-54
references.pmid: 17235301
references.citation: Mol Ther. 2003 Feb;7(2):218-27
references.pmid: 12597910
references.citation: Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7891-6
references.pmid: 9223283
references.citation: EMBO J. 2002 Sep 16;21(18):4989-97
references.pmid: 12234938
references.citation: J Virol. 1998 Nov;72(11):8620-6
references.pmid: 9765401
references.citation: J Gen Virol. 2004 Dec;85(Pt 12):3501-3510
references.pmid: 15557223
references.citation: J Virol. 2008 May;82(10):4974-90
references.pmid: 18337577
references.citation: J Virol. 2006 Aug;80(16):7995-8005
references.pmid: 16873256
references.citation: J Gen Virol. 2009 Sep;90(Pt 9):2209-20
references.pmid: 19515829
references.citation: J Neurovirol. 2002 Dec;8 Suppl 2:103-11
references.pmid: 12491160
references.citation: Virology. 2004 Apr 25;322(1):158-67
references.pmid: 15063125
references.citation: Mol Ther. 2008 Oct;16(10):1727-36
references.pmid: 18728642
references.citation: Mol Ther. 2007 Nov;15(11):2017-26
references.pmid: 17653098
references.citation: Hum Gene Ther. 2003 Jul 20;14(11):1049-63
references.pmid: 12885345
references.citation: Hum Gene Ther. 2007 Feb;18(2):93-105
references.pmid: 17298238
references.citation: J Virol. 2003 Jun;77(11):6567-73
references.pmid: 12743316
references.citation: Nature. 1984 Jun 14-20;309(5969):633-5
references.pmid: 6328323
references.citation: Proc Natl Acad Sci U S A. 2005 May 24;102(21):7571-6
references.pmid: 15897453
references.citation: Virology. 2008 May 10;374(2):487-94
references.pmid: 18279905