title: Involvement of human herpesvirus-6 variant B in classic Hodgkin's lymphoma via DR7 oncoprotein.
abstract: OBJECTIVE
  Hodgkin's lymphoma (HL) is associated with the presence of EBV in Reed-Sternberg (RS) cells in ∼40% of cases. Here, we studied the presence of human herpesvirus type 6 (HHV-6) variant B in RS cells of HL patients and correlated results with clinical parameters. We then examined the implication of HHV-6 DR7B protein in cell deregulation.
  
  
  METHODS
  HHV-6 DR7B protein was produced in a Semliki Forest virus system. Polyclonal antibodies were then generated and used for immunochemical HHV-6 localization in HL biopsies. Binding between DR7B and p53 was studied using a double-hybrid system. Transactivation of NFκB was observed after transient transfection using reporter gene assays. We looked for Id2 factor expression after stable transfection of the BJAB cell line by reverse transcription-PCR and Western blot analysis.
  
  
  RESULTS
  HHV-6 was more common in nodular sclerosis subtype HL, and DR7B oncoprotein was detected in RS cells for 73.7% of EBV-negative patients. Colocalization of EBV and HHV-6 was observed in RS cells of doubly infected patients. DR7B protein bound to human p53 protein. p105-p50/p65 mRNA expression and activation of the NFκB complex were increased when DR7B was expressed. Stable expression of DR7B exhibited a strong and uniform expression of Id2. A slightly higher percentage of remission was observed in patients with RS cells testing positive for DR7B than in those testing negative.
  
  
  CONCLUSIONS
  Collectively, these data provide evidence for the implication of a novel agent, HHV-6, in cases of nodular sclerosis HL.
authors.affiliation: Centre Hospitalier Universitaire Dupuytren, Limoges, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Lacroix
authors.forename: Sophie
authors.initials: S
authors.lastname: Collot-Teixeira
authors.forename: Laurent
authors.initials: L
authors.lastname: Mardivirin
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jaccard
authors.forename: Barbara
authors.initials: B
authors.lastname: Petit
authors.forename: Christophe
authors.initials: C
authors.lastname: Piguet
authors.forename: Franck
authors.initials: F
authors.lastname: Sturtz
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Preux
authors.forename: Dominique
authors.initials: D
authors.lastname: Bordessoule
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ranger-Rogez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015654:Herpesvirus 6, Human / Q000378:metabolism*; D006689:Hodgkin Disease / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism; D009857:Oncogenes; D015534:Trans-Activators / Q000378:metabolism*; D055815:Young Adult
chemical_list: C087150:ORF-1 protein, Human herpesvirus 6; D015534:Trans-Activators