title: Adrenal gland infection by serotype 5 adenovirus requires coagulation factors.
abstract: Recombinant, replication-deficient serotype 5 adenovirus infects the liver upon in vivo, systemic injection in rodents. This infection requires the binding of factor X to the capsid of this adenovirus. Another organ, the adrenal gland is also infected upon systemic administration of Ad, however, whether this infection is dependent on the cocksackie adenovirus receptor (CAR) or depends on the binding of factor X to the viral capsid remained to be determined. In the present work, we have used a pharmacological agent (warfarin) as well as recombinant adenoviruses lacking the binding site of Factor X to elucidate this mechanism in mice. We demonstrate that, as observed in the liver, adenovirus infection of the adrenal glands in vivo requires Factor X. Considering that the level of transduction of the adrenal glands is well-below that of the liver and that capsid-modified adenoviruses are unlikely to selectively infect the adrenal glands, we have used single-photon emission computed tomography (SPECT) imaging of gene expression to determine whether local virus administration (direct injection in the kidney) could increase gene transfer to the adrenal glands. We demonstrate that direct injection of the virus in the kidney increases gene transfer in the adrenal gland but liver transduction remains important. These observations strongly suggest that serotype 5 adenovirus uses a similar mechanism to infect liver and adrenal gland and that selective transgene expression in the latter is more likely to be achieved through transcriptional targeting.
authors: INSERM U948, Nantes, France.
authors: Lucile
authors: L
authors: Tran
authors: Laure-Hélène
authors: LH
authors: Ouisse
authors: Peggy
authors: P
authors: Richard-Fiardo
authors: Philippe R
authors: PR
authors: Franken
authors: Jacques
authors: J
authors: Darcourt
authors: Gaétan
authors: G
authors: Cornilleau
authors: Karim
authors: K
authors: Benihoud
authors: Georges
authors: G
authors: Vassaux
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology*; D000311:Adrenal Glands / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000821:virology*; D000818:Animals; D001779:Blood Coagulation Factors / Q000378:metabolism*; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D007668:Kidney / Q000000981:diagnostic imaging / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D064847:Multimodal Imaging; D011877:Radionuclide Imaging; D014161:Transduction, Genetic; D014859:Warfarin / Q000378:metabolism
chemical_list: D001779:Blood Coagulation Factors; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D014859:Warfarin; D005170:Factor X
references: J Virol. 2007 Sep;81(17):9568-71
references: 17553882
references: Hum Gene Ther. 2002 Sep 20;13(14):1723-35
references: 12396625
references: Am J Physiol Renal Physiol. 2010 Feb;298(2):F454-60
references: 19955188
references: Gene Ther. 2001 Sep;8(17):1347-53
references: 11571572
references: Mol Ther. 2008 Aug;16(8):1474-80
references: 18560416
references: PLoS One. 2012;7(3):e34086
references: 22470517
references: Exp Cell Res. 2006 May 15;312(9):1566-80
references: 16542650
references: J Gene Med. 2009 Nov;11(11):966-77
references: 19670332
references: J Gen Virol. 2000 Nov;81(Pt 11):2605-2609
references: 11038370
references: Gene Ther. 1999 Nov;6(11):1898-903
references: 10602386
references: Blood. 2010 Oct 14;116(15):2656-64
references: 20610817
references: Mol Ther. 2004 Mar;9(3):436-42
references: 15006611
references: Cancer Res. 2004 Nov 1;64(21):8045-51
references: 15520214
references: Gene Ther. 1999 Jul;6(7):1239-48
references: 10455432
references: Mol Ther. 2008 Oct;16(10):1761-9
references: 18714306
references: Clin Cancer Res. 2009 Nov 1;15(21):6595-601
references: 19861465
references: Endocr Rev. 2004 Feb;25(1):1-44
references: 14769826
references: J Virol. 2009 Jul;83(13):6416-28
references: 19369326
references: Cell. 1993 Apr 23;73(2):309-19
references: 8477447
references: Gene Ther. 2007 Dec;14(24):1731-8
references: 17960161
references: Curr Gene Ther. 2009 Apr;9(2):115-27
references: 19355869
references: Mol Ther. 2008 Feb;16(2):302-7
references: 18223549
references: Exp Cell Res. 2006 Apr 1;312(6):817-30
references: 16410001
references: Science. 1997 Feb 28;275(5304):1320-3
references: 9036860
references: J Cell Physiol. 2009 Jul;220(1):45-57
references: 19202555
references: Clin Cancer Res. 2008 Oct 1;14(19):6187-92
references: 18829497
references: Eur J Clin Invest. 2003 Sep;33(9):794-8
references: 12925039
references: Cell. 2002 Sep 20;110(6):789-99
references: 12297051
references: J Virol. 2009 Apr;83(8):3816-25
references: 19158249
references: Hum Gene Ther. 1998 Jan 1;9(1):21-31
references: 9458239
references: Cancer Res. 2004 Jul 15;64(14):4906-11
references: 15256462
references: Endocr Res. 1996 Nov;22(4):631-9
references: 8969922
references: Clin Cancer Res. 2005 Jan 1;11(1):351-60
references: 15671566
references: J Nucl Med. 2012 Dec;53(12):1933-42
references: 23139088
references: Blood. 2006 Oct 15;108(8):2554-61
references: 16788098
references: Cell. 2008 Feb 8;132(3):397-409
references: 18267072
references: Hum Gene Ther. 2005 Feb;16(2):248-61
references: 15761264
references: J Hepatol. 2007 Sep;47(3):396-403
references: 17462783
references: PLoS Pathog. 2010 Oct 07;6(10):e1001142
references: 20949078
references: Mol Imaging. 2003 Jul;2(3):131-7
references: 14649056
references: Cancer Res. 2006 Aug 15;66(16):8233-40
references: 16912203
references: Eur J Nucl Med Mol Imaging. 2010 Jul;37(7):1377-85
references: 20140612
references: Gene Ther. 1999 Sep;6(9):1520-35
references: 10490761
references: Mol Ther. 2011 Jul;19(7):1353-9
references: 21587209
references: Gene Ther. 2008 Feb;15(3):214-23
references: 17989705
references: Gene Ther. 2002 Jun;9(12):769-76
references: 12040458
references: Proc Natl Acad Sci U S A. 2002 May 28;99(11):7484-9
references: 12032309
references: Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15191-6
references: 11734628
references: Am J Physiol Heart Circ Physiol. 2009 Oct;297(4):H1504-13
references: 19684189
references: Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5483-8
references: 18391209