title: Varicella-zoster virus open reading frame 48 encodes an active nuclease.
abstract: Based on a DNA sequence and relative genomic position similar to those other herpesviruses, varicella-zoster virus (VZV) open reading frame 48 (ORF48) is predicted to encode an alkaline nuclease. Here we report the cloning, expression, purification, and characterization of recombinant VZV ORF48 protein and a VZV ORF48 point mutation (T172P). Protein encoded by wild-type ORF48, but not mutant protein, displayed both endo- and exonuclease activity, identifying ORF48 as a potential therapeutic target in VZV disease since efficient viral replication requires viral nuclease activity.
authors: Departments of Ophthalmology.
authors: Niklaus H
authors: NH
authors: Mueller
authors: Don
authors: D
authors: Gilden
authors: Randall J
authors: RJ
authors: Cohrs
mesh_terms: D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D015870:Gene Expression; D014645:Herpesvirus 3, Human / Q000201:enzymology* / Q000235:genetics*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D020125:Mutation, Missense; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012260:Ribonucleases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D016415:Sequence Alignment; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins; D012260:Ribonucleases; C066964:viral alkaline nuclease
references: Int J Biochem Cell Biol. 2007;39(3):606-14
references: 17188926
references: Antiviral Res. 2011 Jun;90(3):242-7
references: 21539861
references: J Gen Virol. 2012 Jan;93(Pt 1):130-138
references: 21900421
references: J Biol Chem. 1978 May 25;253(10):3557-62
references: 206546
references: Curr Top Microbiol Immunol. 1990;154:125-69
references: 2161319
references: J Virol. 1996 Mar;70(3):2008-13
references: 8627727
references: Nature. 1983 Dec 1-7;306(5942):478-80
references: 6316159
references: J Virol. 2009 May;83(10):4952-62
references: 19264771
references: Br J Ophthalmol. 1978 Sep;62(9):581-90
references: 708676
references: EMBO Rep. 2007 Feb;8(2):188-93
references: 17186027
references: J Gen Virol. 1997 Nov;78 ( Pt 11):2953-61
references: 9367383
references: Curr Top Microbiol Immunol. 2010;342:1-14
references: 20225013
references: Ocul Immunol Inflamm. 2011 Jun;19(3):212-3
references: 21595539
references: Nucleic Acids Res. 2011 Jul;39(13):5744-56
references: 21421561
references: J Mol Biol. 1966 Jul;18(2):235-50
references: 5338754
references: Virology. 1996 Jan 15;215(2):152-64
references: 8560762
references: J Neurovirol. 1995 Mar;1(1):130-3
references: 9222350
references: Virology. 1993 Sep;196(1):146-62
references: 8395111
references: J Virol. 2013 Jun;87(12):6943-54
references: 23596286
references: Neurology. 2011 Jul 26;77(4):364-70
references: 21753174
references: J Clin Microbiol. 2001 Aug;39(8):2856-9
references: 11474003
references: Nucleic Acids Res. 1989 Oct 11;17(19):7609-22
references: 2552412
references: Trans Am Ophthalmol Soc. 1942;40:390-439
references: 16693295
references: J Virol. 2004 May;78(9):4599-608
references: 15078942
references: Br J Pharmacol. 2008 Sep;155(2):227-35
references: 18552872
references: Virology. 1998 May 10;244(2):442-57
references: 9601512
references: J Virol. 2009 Mar;83(6):2601-10
references: 19129438
references: J Neurovirol. 2010 Nov;16(6):411-8
references: 20874010
references: J Gen Virol. 1990 Dec;71 ( Pt 12):2941-52
references: 2177086
references: J Gen Virol. 1986 Sep;67 ( Pt 9):1759-816
references: 3018124
references: J Biol Chem. 2004 Apr 9;279(15):14734-45
references: 14736888