Cancer Res Treat.  2005 Oct;37(5):257-267.

Epstein-Barr Virus in Human Malignancy: A Special Reference to Epstein-Barr Virus associated Gastric Carcinoma

• Chang MS
• Kim WH

Abstract

Epstein-Bar virus (EBV), a human herpesvirus, establishes a life-long persistent infection in 90~95% of human adult population worldwide. EBV is the etiologic agent of infectious mononucleosis, and EBV is associated with a variety of human malignancy including lymphoma and gastric carcinoma. Recently, EBV has been classified as group 1 carcinogen by the WHO International Agency for Research on Cancer. Evidence is presented which suggests that failures of the EBV-specific immunity may play a role in the pathogenesis of EBV-associated malignancy. At present, the precise mechanisms by which EBV transforms B lymphocytes have been disclosed. Encouragingly, they have had enough success so far to keep them enthusiastic about novel therapeutic trial in the field of EBV-associated lymphoma. However, information on EBV-associated gastric carcinoma is still at dawn. This article reviews EBV biology, immunological response of EBV infection, unique oncogenic property of EBV, peculiarity of EBV-associated gastric carcinoma, and lastly, EBV-targeted therapy and vaccination.

Keyword

Human herpes virus 4; Epstein-Barr virus (EBV); Oncogenic virus; Stomach neoplasms; Lymphoma; EBV-targeted treatment

MeSH Terms

Adult
B-Lymphocytes
Biology
Epstein-Barr Virus Infections
Herpesvirus 4, Human*
Humans*
Infectious Mononucleosis
International Agencies
Lymphoma
Oncogenic Viruses
Stomach Neoplasms
Vaccination

Figure

• 

  Fig. 1 Map of the B95-8 EBV genome. Vertical lines indicate BamHI restriction sites. By convention, the restriction fragments are designated alpbabetically, with the A fragment being the largest, the B fragment the next largest, and so on. Open reading frames are identified by making reference to the appropriate BamHI restriction fragment. Thus, BKRF1 indicates the BamHI-K fragment, rightward open reading frame, 1 (EBNA-1). (Source: Ref. 12)

• 

  Fig. 2 EBV episome, transcripts, mRNAs, and proteins in type III latent infection. Largely unique (U1-U5) and highly repetitive internal (IR1-4) or terminal repeat (TR) DNA domains, the episomal replicon (ori P), and the location of exons encoding EBV nuclear proteins (EBNA 1, 2, 3A, 3B, 3C, and LP) or membrane proteins (LMP 1, 2A, or 2B) genes are indicated. (Source: Ref.12)

• 

  Fig. 3 The four pathways by which the EBV latent membrane protein 1 (LMP1) is thought to signal inside cells. LMP1 mediates nuclear factor κB (NF-κB) signaling through both the C-terminal activating region 1 (CTAR1) and CTAR2 domains via tumor necrosis factor receptor (TNFR) associated factor (TRAF) molecules. The TNFR associated death domain (TRADD)-TRAF2 complex, which binds to CTAR2, also activates the C-Jun N-terminal kinase (JNK)-AP-1 pathway. Both CTAR1 and CTAR2 use TRAF2 to signal via the p38/MAPK (mitogen activated protein kinase) axis. The recently identified box 1 and box 2 motifs (CTAR3) activate the Janus kinas (JAK)-STAT pathway. The net result of signaling along these pathways is the regulation of transcription of various cellular genes and is responsible for many of the pleiotropic effects of LMP1. (Source: Ref.32)

• 

  Fig. 4 In situ hybridization of Epstein-Barr virus encoded small RNAs (EBER) in gastric cancer. This reveals specific EBER signals in nearly all of cancer cell nuclei. (A) Poorly differentiated adenocarcinoma, (B) Well differentiated adenocarcinoma. (C) Gastric carcinoma with lymphoid stroma. Note a few signals in the surrounding lymphoid stroma, while EBER are localized over the nuclei of all the cancer cell nuclei. (Source: Ref.34,40)

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