[Expression of ZEBRA protein of Epstein-Barr virus in Hungarian patients with Hodgkin lymphoma: latent or lytic cycle?].
BACKGROUND
Epstein-Barr virus is a ubiquitous human herpes virus in the Hungarian population. The virus is associated with an increasing number of lymphoid malignancies, such as Hodgkin and non-Hodgkin lymphomas. The ability of the virus to establish life-long persistent infection and induce growth transformation is related to the viral proteins that are variously expressed in both normal and malignant cells. Although the presence of ZEBRA protein induces lytic cycle, some lymphoma cases show this protein expression.


OBJECTIVE
In our present study we investigated the frequency of expression of ZEBRA protein in Hungarian patients with Hodgkin lymphoma associated with Epstein-Barr virus infection. The authors wanted to clarify whether this expression is specific to latency type II or occurs in some non-Hodgkin lymphoma cases with latency type III as well. Does the expression of ZEBRA protein have any effect on therapeutic response and survival rate of the patients?


METHODS
109 HL and 59 NHL were studied for the presence of the virus in the tumor and for expression of the latency proteins and ZEBRA by immunohistochemistry.


RESULTS
25 samples were evaluated successfully for ZEBRA of the 47 LMP1 positive HL samples. We detected the weak expression of ZEBRA protein in 13 of the 25 LMP1 positive Hodgkin lymphoma cases and in 6 of the 18 LMP1 positive non-Hodgkin lymphoma samples. The authors could not find correlation between the expression of ZEBRA protein and the type of latency. During the followed 120 months the total survival of patients with ZEBRA positivity proved to be significantly shorter as compared to that of ZEBRA negative cases. The authors could not find significant difference in the uneventful survival of these two groups.


CONCLUSIONS
In the examined group of patients the ZEBRA positivity associated with a poor prognosis of the disease. Besides this relatively small number of cases, additional extensive studies are needed to conclude our observation. Elucidation of the switching mechanisms by which Epstein-Barr virus induces lytic cycle may provide an efficacious therapeutic approach to the EBV-related malignancies.
Beck
Zoltán
Z
Debreceni Egyetem, Orvos és Egészségtudományi Centrum, Altalános Orvostudományi Kar, Orvosi Mikrobiológiai Intézet.
Illés
Arpád
A
Keresztes
Katalin
K
Bessenyei
Beáta
B
Szöllosi
Zoltán
Z
Kis
Andrea
A
Oláh
Eva
E
D000328:Adult; D000368:Aged; D004268:DNA-Binding Proteins / Q000032:analysis*; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006689:Hodgkin Disease / Q000378:metabolism* / Q000628:therapy / Q000821:virology*; D006801:Humans; D006814:Hungary; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D015534:Trans-Activators / Q000032:analysis*; D016896:Treatment Outcome; D014763:Viral Matrix Proteins / Q000032:analysis; D014764:Viral Proteins / Q000032:analysis*
C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D015534:Trans-Activators; D014763:Viral Matrix Proteins; D014764:Viral Proteins