Antibody against the Epstein-Barr virus BHRF1 protein, a homologue of Bcl-2, in patients with nasopharyngeal carcinoma

Abstract

The Epstein-Barr virus (EBV) open reading frame BHRF1, a homologue of the oncogene bcl-2, was cloned from a patient with nasopharyngeal carcinoma (NPC) and overexpressed in Escherichia coli. The resulting recombinant BHRF1 fusion protein, with an apparent molecular weight of 35 KD, was used as antigen in an immunoblotting assay for IgG antibody in human sera. Anti-BHRF1 antibody was detected in 57 (61.3%) of 93 patients with NPC, 5 (5.7%) of 87 patients with nonmalignant diseases of the nasopharynx, and in 1 (1.3%) of 78 healthy blood donors. The positivity rate in these nonmalignant patients was 4.4 times that of the normal controls. Negative results were observed in four patients with infectious mononucleosis and patients with other cancers, including 4 with esophageal cancer, 11 with lung cancer, 10 with lymphoma, 13 with gastric carcinoma, 10 with cervical carcinoma, and 10 with other head and neck cancers. Antibody neutralizing EBV DNase and IgA antibody to viral capsid antigen (VCA) were assayed in parallel. The results showed that 7.5% of the NPC patients were negative for anti-DNase and anti-VCA antibodies and EBV infection could be detected by the anti-BHRF1 antibody alone. The demonstration of anti-BHRF1 antibody in most NPC sera strongly supports the hypothesis that the EBV BHRF1 protein is expressed in most NPC patients and its specific antibody can be a useful marker for the diagnosis of NPC.

Epstein–Barr virus latent membrane protein 1 induces micronucleus formation, represses DNA repair and enhances sensitivity to DNA-damaging agents in human epithelial cells

“…Further studies indicated that antibodies against EBV could be useful markers for the early detection of NPC patients (Henle and Henle, 1976;Zeng et al, 1982). In our laboratory, we have examined the antibodies against EBV DNase, DNA polymerase, thymidine kinase, major DNA binding protein, BHRF1, viral capsid antigen (VCA) and ENBA1 in patients and controls, and found that all these antibodies could be useful markers for the detection of NPC (Chen et al, 1982(Chen et al, , 1985(Chen et al, , 1989Liu et al, 1989Liu et al, , 1997Liu et al, , 1998Hsu et al, 1992). Among these was a prospective study carried out between 1983 and 1986 to examine the antibodies against EBV DNase and VCA in the inhabitants of NPC high-risk areas in Taiwan (Chen et al, 1989).…”

Improved Accuracy of Detection of Nasopharyngeal Carcinoma by Combined Application of Circulating Epstein–Barr Virus DNA and Anti-Epstein–Barr Viral Capsid Antigen IgA Antibody

“…These were based on antibodies to different antigenic components of the EBV (9,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Attempts to use panels of antibody-based markers have generally been useful in improving the accuracy of NPC detection (13, 15, 20, 21, 29 -32 ).…”

From Anti-EBV Immune Responses to the EBV Diseasome via Cross-reactivity

“…Such cross-reactive potential explains why higher the anti-EBV IgG antibody titer, worse may be the disease prognosis and faster the disease progression as described by a continuum of reports since the 1970s. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] That is, autoimmunity is not a matter of "rare immunological holes," but it is intrinsic to the immune response that involves most of the human proteome by being most of the human proteome shared with microbial entities as a result of a long evolutionary path that from viruses and bacteria led to the eukaryotic cell. 180 In conclusion, this study highlights the necessity of reviewing the hypothesis of the "negative selection" of self-reactive lymphocytes and, at the same time, emphasizes the importance of the "peptide uniqueness" concept to develop immunotherapies against EBV infection, and infections in general.…”

“…[9][10][11][12][13][14] At the same time, anti-EBV antibody level was found to be higher in BL patients than in control subjects. 3,[15][16][17] High level of anti-EBV immunoglobulin G antibodies were also found in subjects with NPC, [18][19][20][21] with IgG reactivity increasing significantly with tumor stage 21 ; Hodgkin and non-Hodgkin lymphomas [22][23][24] ; precancerous gastric lesions 25 ; MS [26][27][28][29] ; RA [30][31][32] ; MG 33,34 ; and SLE, 29,31,34 among others. In general, high antibody titers to EBV appeared to be related to a worse prognosis, a phenomenon that has been described by Coutinho's laboratory 35 as "the advantage of being low-respondents."…”