title: Characterization of variants in the promoter of BZLF1 gene of EBV in nonmalignant EBV-associated diseases in Chinese children.
abstract: BACKGROUND
  Diseases associated with Epstein-Barr virus (EBV) infections, such as infectious mononucleosis (IM), EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV) are not rare in Chinese children. The association of type 1 or type 2 EBV and variants of the EBV BZLF1 promoter zone (Zp) with these diseases is unclear.
  
  
  RESULTS
  The objective of this study was to investigate the relationship between EBV genotypes (Zp variants and EBV type 1 and 2) and the clinical phenotypes of EBV-associated diseases in Chinese children. The Zp region was directly sequenced in 206 EBV-positive DNA samples from the blood of patients with IM, EBV-HLH, CAEBV, and healthy controls. Type 1 or type 2 EBV was examined by PCR for EBNA2 and EBNA3C subtypes. Four polymorphic Zp variants were identified: Zp-P, Zp-V3, Zp-P4 and Zp-V1, a new variant. The Zp-V3 variant was significantly associated with CAEBV (P <or= 0.01). The frequency of co-infection with Zp variants was higher in patients with CAEBV and EBV-HLH, compared with IM and healthy controls, mostly as Zp-P+V3 co-infection. Type 1 EBV was predominant in all categories (81.3-95%) and there was no significant difference in the frequency of the EBV types 1 and 2 in different categories (P > 0.05).
  
  
  CONCLUSIONS
  Type 1 EBV and BZLF1 Zp-P of EBV were the predominant genotypes in nonmalignant EBV associated diseases in Chinese children and Zp-V3 variant may correlates with the developing of severe EBV infection diseases, such as CAEBV and EBV-HLH.
authors.affiliation: Department of Infection, Beijing Children's Hospital, The Capital Medical University, Beijing, China.
authors.forename: Yingkang
authors.initials: Y
authors.lastname: Jin
authors.forename: Zhengde
authors.initials: Z
authors.lastname: Xie
authors.forename: Gen
authors.initials: G
authors.lastname: Lu
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
authors.forename: Kunling
authors.initials: K
authors.lastname: Shen
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002681:China; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000473:pathology* / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics*
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; D004279:DNA, Viral; D015534:Trans-Activators
references.citation: Blood. 1996 Nov 1;88(9):3491-501
references.pmid: 8896415
references.citation: Scand J Infect Dis. 1987;19(3):373-9
references.pmid: 3039653
references.citation: Arch Pathol Lab Med. 1991 May;115(5):470-4
references.pmid: 1850588
references.citation: J Virol. 1990 Sep;64(9):4084-92
references.pmid: 2166806
references.citation: Pediatr Blood Cancer. 2007 Feb;48(2):124-31
references.pmid: 16937360
references.citation: J Virol. 2000 Feb;74(4):1801-9
references.pmid: 10644353
references.citation: J Gen Virol. 1991 Oct;72 ( Pt 10):2399-409
references.pmid: 1681026
references.citation: J Natl Cancer Inst. 2002 Dec 4;94(23):1757-63
references.pmid: 12464647
references.citation: Blood. 2001 Jul 15;98(2):280-6
references.pmid: 11435294
references.citation: J Virol. 1996 Oct;70(10):7301-5
references.pmid: 8794387
references.citation: J Gen Virol. 1999 Feb;80 ( Pt 2):441-445
references.pmid: 10073706
references.citation: Blood. 1996 Jul 1;88(1):242-51
references.pmid: 8704180
references.citation: Oncogene. 1992 Nov;7(11):2131-40
references.pmid: 1331932
references.citation: J Infect. 2007 Mar;54(3):298-306
references.pmid: 16784778
references.citation: Proc Natl Acad Sci U S A. 1984 Dec;81(23):7632-6
references.pmid: 6209719
references.citation: Am J Hematol. 2005 Sep;80(1):64-9
references.pmid: 16138335
references.citation: J Natl Cancer Inst. 2003 Jul 2;95(13):1008-9; author reply 1009
references.pmid: 12837838
references.citation: Int J Hematol. 1997 Aug;66(2):135-51
references.pmid: 9277044
references.citation: Br Med J (Clin Res Ed). 1983 Jul 9;287(6385):85-8
references.pmid: 6222781