title: VP23R of infectious spleen and kidney necrosis virus mediates formation of virus-mock basement membrane to provide attaching sites for lymphatic endothelial cells.
abstract: Putative open reading frames (ORFs) encoding laminin-like proteins are found in all members of the genus Megalocytivirus, family Iridoviridae. This is the first study that identified the VP23R protein encoded by ORF23R of the infectious spleen and kidney necrosis virus (ISKNV), a member of these genes of megalocytiviruses. The VP23R mRNA covering the ISKNV genomic coordinates 19547 to 22273 was transcribed ahead of the major capsid protein. Immunofluorescence analysis demonstrated that VP23R was expressed on the plasma membrane of the ISKNV-infected cells and could not be a viral envelope protein. Residues 292 to 576 of VP23R are homologous to the laminin γ1III2-6 fragment, which covers the nidogen-binding site. An immunoprecipitation assay showed that VP23R could interact with nidogen-1, and immunohistochemistry showed that nidogen-1 was localized on the outer membrane of the infected cells. Electron microscopy showed that a virus-mock basement membrane (VMBM) was formed on the surface of the infected cells and a layer of endothelial cells (ECs) was attached to the VMBM. The VMBM contained VP23R and nidogen-1 but not collagen IV. The attached ECs were identified as lymphatic endothelial cells (LECs), which have unique feature of overlapping intercellular junctions and can be stained by immunohistochemistry using an antibody against a specific lymphatic marker, Prox-1. Such infection signs have never been described in viruses. Elucidating the functions of LECs attached to the surface of the infected cells may be useful for studies on the pathogenic mechanisms of megalocytiviruses and may also be important for studies on lymphangiogenesis and basement membrane functions.
authors.affiliation: Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Xu
authors.forename: Shaoping
authors.initials: S
authors.lastname: Weng
authors.forename: Ting
authors.initials: T
authors.lastname: Lin
authors.forename: Junliang
authors.initials: J
authors.lastname: Tang
authors.forename: Lichao
authors.initials: L
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yu
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Huang
authors.forename: Jianguo
authors.initials: J
authors.lastname: He
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001485:Basement Membrane / Q000821:virology*; D004266:DNA Virus Infections / Q000662:veterinary* / Q000821:virology; D042783:Endothelial Cells / Q000821:virology*; D005393:Fish Diseases / Q000821:virology*; D005399:Fishes; D007497:Iridoviridae / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053585:Virus Attachment
chemical_list: D014764:Viral Proteins
references.citation: Anat Rec. 1989 Apr;223(4):376-83
references.pmid: 2712351
references.citation: J Biol Chem. 1994 Jul 22;269(29):19167-75
references.pmid: 8034675
references.citation: Int J Oncol. 2009 Mar;34(3):673-80
references.pmid: 19212672
references.citation: J Am Soc Nephrol. 1995 Oct;6(4):1178-85
references.pmid: 8589284
references.citation: J Cell Biol. 2004 Mar 29;164(7):959-63
references.pmid: 15037599
references.citation: J Cell Sci. 2001 Mar;114(Pt 6):1137-44
references.pmid: 11228157
references.citation: Pediatr Dermatol. 1996 Jan-Feb;13(1):5-9
references.pmid: 8919515
references.citation: J Virol. 2008 May;82(9):4371-83
references.pmid: 18305039
references.citation: Matrix. 1993 May;13(3):215-22
references.pmid: 8326911
references.citation: Lymphology. 1989 Mar;22(1):31-5
references.pmid: 2725055
references.citation: Virology. 2008 Jun 20;376(1):1-12
references.pmid: 18423508
references.citation: J Gen Virol. 2006 Oct;87(Pt 10):2907-2915
references.pmid: 16963749
references.citation: PLoS One. 2009 Sep 17;4(9):e7067
references.pmid: 19759906
references.citation: J Biochem. 1996 Jul;120(1):133-7
references.pmid: 8864855
references.citation: Dis Aquat Organ. 2008 Jan 24;78(3):209-15
references.pmid: 18380219
references.citation: Virology. 1983 Apr 30;126(2):466-79
references.pmid: 6857994
references.citation: Virology. 2001 Dec 5;291(1):126-39
references.pmid: 11878882
references.citation: Am J Pathol. 2000 Jun;156(6):1901-10
references.pmid: 10854213
references.citation: Crit Rev Biochem Mol Biol. 1992;27(1-2):93-127
references.pmid: 1309319
references.citation: Mol Cell Probes. 2006 Jun-Aug;20(3-4):212-22
references.pmid: 16697343
references.citation: Science. 2000 Apr 7;288(5463):150-4
references.pmid: 10753123
references.citation: Lymphology. 1987 Dec;20(4):257-66
references.pmid: 2451095
references.citation: Development. 1997 Feb;124(3):683-91
references.pmid: 9043083
references.citation: Kidney Int. 1993 Jan;43(1):7-12
references.pmid: 8433572
references.citation: FASEB J. 2005 Jun;19(8):1027-9
references.pmid: 15774577
references.citation: N Engl J Med. 2003 Jun 19;348(25):2543-56
references.pmid: 12815141
references.citation: Adv Virus Res. 1996;46:345-412
references.pmid: 8824704
references.citation: J Virol. 1984 Feb;49(2):609-14
references.pmid: 16789247
references.citation: J Clin Invest. 2005 Sep;115(9):2363-72
references.pmid: 16138190
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12573-9
references.pmid: 19633189
references.citation: Development. 2004 Apr;131(7):1619-28
references.pmid: 14998921
references.citation: J Biol Chem. 1993 Dec 15;268(35):26033-6
references.pmid: 8253711
references.citation: Arch Dermatol. 1992 Aug;128(8):1078-82
references.pmid: 1497362
references.citation: Virology. 1997 Apr 14;230(2):207-16
references.pmid: 9143276
references.citation: Nat Med. 2006 Feb;12(2):230-4
references.pmid: 16415878
references.citation: J Biol Chem. 1990 Jun 25;265(18):10597-603
references.pmid: 2191952
references.citation: Arch Virol. 2007;152(4):763-73
references.pmid: 17131065
references.citation: J Cell Biol. 1992 Jun;117(5):1119-33
references.pmid: 1577869
references.citation: Cell. 2010 Feb 19;140(4):460-76
references.pmid: 20178740
references.citation: EMBO J. 1993 May;12(5):1879-85
references.pmid: 8491180
references.citation: J Biol Chem. 1993 May 25;268(15):10881-7
references.pmid: 8496153
references.citation: Science. 2010 Jan 1;327(5961):88-92
references.pmid: 20044576
references.citation: Matrix Biol. 2004 Jan;22(7):521-38
references.pmid: 14996432
references.citation: J Cell Biol. 1991 Dec;115(5):1383-95
references.pmid: 1955479
references.citation: Lymphology. 2005 Dec;38(4):159-66
references.pmid: 16515224
references.citation: J Cell Biol. 2005 Apr 11;169(1):179-89
references.pmid: 15824137
references.citation: Development. 2002 Jun;129(11):2711-22
references.pmid: 12015298
references.citation: Cell Cycle. 2005 Feb;4(2):228-30
references.pmid: 15655347
references.citation: J Clin Invest. 1992 Dec;90(6):2251-7
references.pmid: 1469085
references.citation: EMBO J. 1994 Aug 15;13(16):3741-7
references.pmid: 8070402
references.citation: Curr Opin Lipidol. 2007 Oct;18(5):540-5
references.pmid: 17885425
references.citation: Ann N Y Acad Sci. 1998 Oct 23;857:130-42
references.pmid: 9917838
references.citation: J Exp Med. 2005 Apr 4;201(7):1089-99
references.pmid: 15809353
references.citation: Curr Opin Cell Biol. 1989 Oct;1(5):983-8
references.pmid: 2697299
references.citation: Virus Res. 2008 Aug;135(2):273-81
references.pmid: 18485510
references.citation: WormBook. 2005 Sep 01;:1-15
references.pmid: 18050423
references.citation: J Biomech Eng. 2003 Jun;125(3):407-14
references.pmid: 12929246
references.citation: FEBS Lett. 2006 Apr 17;580(9):2253-7
references.pmid: 16574105
references.citation: Biochem J. 2003 Apr 15;371(Pt 2):289-99
references.pmid: 12519075
references.citation: Virology. 1985 Oct 30;146(2):292-301
references.pmid: 2996221
references.citation: Nat Rev Cancer. 2003 Jun;3(6):422-33
references.pmid: 12778132
references.citation: Int J Oncol. 2003 Aug;23(2):533-9
references.pmid: 12851706
references.citation: J Mol Med (Berl). 2007 Aug;85(8):825-36
references.pmid: 17426950