Expression of Epstein‐Barr virus‐encoded proteins in nasopharyngeal carcinoma

Abstract

Expression of the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNA 1 to 6) and membrane-associated protein (LMP) was investigated by immunoblotting in 83 nasopharyngeal carcinoma (NPC) biopsies and 25 other tumor and normal tissue specimens from the head and neck region. Fifty-eight of the 83 NPC biopsies were large enough to yield parallel data on virus DNA and viral expression. All 16 cases of clinically diagnosed and histologically confirmed NPCs from North Africa contained EBV DNA and expressed EBNA-1. Of 31 clinically diagnosed NPCs from China, 29 contained EBV DNA and 25 of these expressed EBNA-1. One control tissue biopsy from the oropharynx of NPC patients contained EBV DNA, but none expressed EBNA-1. The latent membrane protein (LMP) was detected in 22/31 of the Chinese and in 10/16 of the North African NPC biopsies. None of the NPC biopsies or control tissues expressed detectable amounts of EBNA 2 or any of the other 4 nuclear antigens which are invariably expressed in EBV-transformed B cells. A smaller number of tumors from Malaysia and East Africa exhibited a similar pattern of expression. EBV was rescued from a nude-mouse-passaged North African NPC tumor by co-cultivation of the tumor cells with umbilical cord blood lymphocytes. The tumor expressed EBNA 1 and LMP, but not EBNA 2 or the other 4 EBNAs. The resulting LCLs expressed all 6 nuclear antigens, EBNA 1 to 6 and LMP. Our data suggest that expression of the EBV genome is regulated in a tissue-specific fashion.

Transcriptional activation of NF-κB activity by Epstein–Barr virus (EBV) LMP1 as a selective therapeutic strategy for EBV-associated diseases

“…Only two virally encoded proteins, the EBV-encoded nuclear antigen 1 (EBNA1) and the latent membrane protein 1 (LMP1), have been detected in NPC biopsies by Western blot analysis. 2 Biologically, EBNA1 is an EBV-encoded transactivator and is required in trans to maintain the virus genome in an episomal form. 3 LMP1 is an integral membrane protein and has a profound effect on the morphology of rodent cells, indicating that the protein is potentially oncogenic.…”

Establishment of a monkey kidney epithelial cell line with the BARF1 open reading frame from Epstein-Barr Virus

“…Since no suitable system has so far been developed for infecting epithelial cells with EBV, no direct evidence has yet been reported on EBV ability to immortalize epithelial cells. While EBNA 2 is a key element of B cell growth transformation (Cohen et al, 1989), its expression was not detected in NPC biopsies or NPC derived epithelial cells (Fahraeus et al, 1988;Hitt et al, 1989;Young et al, 1988). By contrast, three latent genes: EBNA1, LMP1 and LMP2, were shown to be transcribed in NPC biopsies (Fahraeus et al, 1988;Hitt et al, 1989;Young et al, 1988;Brooks et al, 1992;Busson et al, 1992).…”

“…While EBNA 2 is a key element of B cell growth transformation (Cohen et al, 1989), its expression was not detected in NPC biopsies or NPC derived epithelial cells (Fahraeus et al, 1988;Hitt et al, 1989;Young et al, 1988). By contrast, three latent genes: EBNA1, LMP1 and LMP2, were shown to be transcribed in NPC biopsies (Fahraeus et al, 1988;Hitt et al, 1989;Young et al, 1988;Brooks et al, 1992;Busson et al, 1992). LMP1 may be important in NPC development since this latent gene, ®rst found to induce malignant transformation in established rodent ®broblasts (Wang et al, 1985;Baichwal and Sugden, 1988), was recently shown to inhibit di erentiation (Dawson et al, 1990) and cause morphological change with reduced cytokeratin expression in human epithelial cells (Fahraeus et al, 1990;Niedobitek et al, 1992).…”

In vitro EBV-infected subline of KMH2, derived from Hodgkin lymphoma, expresses only EBNA-1, while CD40 ligand and IL-4 induce LMP-1 but not EBNA-2

“…2 The type II latency pattern was first seen in EBV carrying nasopharyngeal carcinoma (NPC). 10 In addition to HL, it occurs also in T and NK lymphomas. In Burkitt lymphomas (BLs) and in the EBV-carrying memory B cells of healthy individuals, only one viral protein, EBNA-1, is expressed.…”