Pathogenesis and Chemotherapy of Herpesvirus Infection

National Institute Of Allergy And Infectious Diseases

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Abstract

Epstein Barr virus (EBV) is associated with 200,000 cases of cancer each year worldwide and is the cause of infectious mononucleosis. The virus is associated with nasopharyngeal carcinoma, gastric carcinoma, Burkitt lymphoma, and Hodgkin disease. The virus causes lymphomas in some persons who have bone marrow or solid organ transplants. Immunodeficient patients with mutations in specific genes, can develop lymphoproliferation associated with EBV or EBV-positive B cell lymphomas. Gastric carcinoma (GC) is the third leading cause of cancer mortality worldwide, with an estimated 783,000 deaths and more than 1 million new diagnoses in 2018. EBV is present in about 9-10% of gastric carcinomas. Worldwide, gastric carcinomas are the most common EBV associated malignancy. EBV-positive gastric carcinomas are a distinct subtype of gastric cancer that has lower mortality and occurs more frequently in cases among males than females. In FY 2021, we analyzed plasma samples from EBV-positive and EBV-negative gastric carcinoma patients for antibodies to 85 EBV proteins. Antibodies with 20% sensitivity at 95% specificity for tumor EBV status were verified by additional assays in independent samples from another cohort. We found 9 EBV antibodies that were present at higher levels in patients with EBV-positive gastric carcinoma, but absent in persons with EBV-negative gastric carcinoma. Seven of these were verified using other antibody assays. The top three EBV proteins that these antibodies were directed against in EBV-positive gastric carcinoma were EBV LF2, BORF2, and BALF2 and the odds of having an EBV-positive gastric carcinoma were >40 times the odds of having an EBV-negative gastric carcinoma based on the level of each of these antibodies. The presence of antibodies found primarily in patients with EBV-positive gastric carcinoma might be useful for screening for cancer, epidemiologic studies, and immune-based treatment of EBV-positive gastric carcinoma.