Involvement of human herpesvirus-6 variant B in classic Hodgkin's lymphoma via DR7 oncoprotein.
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.
Lacroix
Aurélie
A
Centre Hospitalier Universitaire Dupuytren, Limoges, France.
Collot-Teixeira
Sophie
S
Mardivirin
Laurent
L
Jaccard
Arnaud
A
Petit
Barbara
B
Piguet
Christophe
C
Sturtz
Franck
F
Preux
Pierre-Marie
PM
Bordessoule
Dominique
D
Ranger-Rogez
Sylvie
S
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
C087150:ORF-1 protein, Human herpesvirus 6; D015534:Trans-Activators