Purpose: EBV has been associated with nasopharyngeal carcinomas (NPC). In North Africa, the incidence is bimodalöthe first peak occurring at f20 years of age and the second peak occurring at f50 years. Standard diagnostic tests based on immunofluorescence using anti-IgA EBV have shown that young North African patients have a negative serology compared with older patients.We are interested in two EBV-encoded oncoproteins, LMP1and BARF1, which have thus far not been studied in terms of their potential as diagnostic markers for NPC. These two viral oncoproteins have been detected in cell culture media, so we tested whether they could be detected in the serum and saliva of patients with NPC. Experimental Design: LMP1 and BARF1 proteins were analyzed in the sera and saliva of young patients and adult patients with NPC from North Africa and China. We then examined whether the secreted proteins had biological activity by analyzing their mitogenic activity. Results: Both LMP1 and BARF1 were present in the serum and saliva from North African and Chinese patients with NPC. All young North African patients secreted both proteins, whereas 62% and 100% of adult patients secreted LMP1 and BARF1, respectively. From animal studies, the secreted LMP1was associated with exosome-like vesicles. These secreted EBV oncoproteins showed a powerful mitogenic activity in B cells. Conclusion: Both proteins will be a good diagnostic marker for NPC whereas BARF1is a particularly promising marker for all ages of patients with NPC. Their mitogenic activity suggests their implication in the oncogenic development of NPC. Nasopharyngeal carcinoma (NPC) is a human malignancyderived from the epithelium of the nasopharyngeal cavity. It is one of the most striking examples of a human malignancy that is consistently associated with a virus (1 -3). The EBV genome is contained in all malignant NPC cells and it encodes viral proteins that contribute to the malignant phenotype (4 -6). Even though infection with EBV is ubiquitous in humans, the incidence of NPC is extremely variable, depending on the geographic area. Whereas the incidence of NPCs in the Chinese population peaks at f50 years of age, there are two peaks of incidence in North Africa-one at f20 years of age and the second at f50 years of age (6). Because of the close association of EBV with NPC, detection of EBV anti-IgA, anti-EA, or anti-VCA by immunofluorescence tests in serum from patients with NPC is used in most Asian countries. However, this test is almost always negative for young North African patients (6). Recent data showed a successful diagnosis of NPC by molecular serology based on EBV-encoded proteins, DNase, thymidine kinase, and p16 VCA used as viral antigens (7 -10). Virus load in patient blood has been used as a diagnostic marker for NPC (11,12), but high levels have been reported in nonneoplastic disorders, gastrointestinal malignancies, and for lymphoproliferative disease (13,14). We therefore need a more reliable, simpler, and specific diagnostic test for NPC.Seve...

BackgroundDespite the fact that the implication of human papillomavirus (HPV) in the carcinogenesis and prognosis of cervical cancer is well established, the impact of a co-infection with high risk HPV (HR-HPV) and Epstein-Barr virus (EBV) is still not fully understood.MethodsFifty eight randomly selected cases of squamous cell carcinomas (SCC) of the uterine cervix, 14 normal cervices specimens, 21 CIN-2/3 and 16 CIN-1 cases were examined for EBV and HPV infections. Detection of HR-HPV specific sequences was carried out by PCR amplification using consensus primers of Manos and by Digene Hybrid Capture. The presence of EBV was revealed by amplifying a 660 bp specific EBV sequence of BALF1. mRNA expression of LMP-1 in one hand and protein levels of BARF-1, LMP-1 and EBNA-1 in the other hand were assessed by RT-PCR and immunoblotting and/or immunohischemistry respectively.ResultsHR-HPV infection was found in patients with SCC (88%), low-grade (75%) and high grade (95%) lesions compared to only 14% of normal cervix cases. However, 69%, 12.5%, 38.1%, and 14% of SCC, CIN-1, CIN-2/3 and normal cervix tissues, respectively, were EBV infected. The highest co-infection (HR-HPV and EBV) was found in squamous cell carcinoma cases (67%). The latter cases showed 27% and 29% expression of EBV BARF-1 and LMP-1 oncogenes respectively.ConclusionThe high rate of HR-HPV and EBV co-infection in SCC suggests that EBV infection is incriminated in cervical cancer progression. This could be taken into account as bad prognosis in this type of cancer. However, the mode of action in dual infection in cervical oncogenesis needs further investigation.

The genotypes of Epstein-Barr virus (EBV) were investigated in North African nasopharyngeal carcinoma (NPC) biopsies, nasopharyngeal chronic inflammation (NCI) biopsies, and saliva of healthy individuals from Algeria and Tunisia where there is an intermediate incidence of NPC. The prevalence of A-type virus in NPC, NCI biopsies and saliva of healthy individuals was found in these regions by means of a PCR assay. Restriction enzyme polymorphism analysis by Southern blotting revealed that all North African EBV variants have a conserved restriction site on BamHI W'-I' and XhoI LMP gene. No additional BamHI enzyme site on the BamHI-F fragment was observed; however, the presence of an extra BamHI site on the BamHI-H fragment giving 2 HI and H2 fragment-like EBV M-ABA strains was found. All EBV strains present in NPC or NCI biopsies at all ages were homogeneous in these polymorphisms and no correlation was observed between the EBV genotypes from NPC patients and clinical stages of the cancer. These characteristics revealed a significant difference between the EBV variants common in Chinese NPC and those in North African NPC.

A waterborne epidemic of non-A, non-B hepatitis occurred in Medea, an Algerian town of 68,000 inhabitants during the autumn and winter of 1980-1981. About 6 weeks before the epidemic, there had been a chlorination failure and an accidental sewage contamination of the river water that supplied large parts of the town. From October, 1980, to January, 1981, 788 cases were notified. This epidemic affected mostly young adults, who usually recovered; however, a high rate of mortality was noted among pregnant women (nine patients, nine deaths). Serological examinations performed on 57 hospitalized patients excluded both hepatitis A and B. The waterborne nature of the epidemic was suggested by a study of the case distribution according to water supplies. The epidemic was severe in the areas supplied by the untreated river water. Few cases were reported in the areas receiving spring water, where chlorination never failed. A mild incidence of infection was noted in the areas supplied by a mixture of untreated river water and chlorinated spring water.

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