Molecular Methods for Detecting Epstein-Barr Virus (Part I): In Situ Hybridization to Epstein-Barr Virus-Encoded RNA (EBER) Transcripts

In situ hybridization (ISH) to Epstein-Barr virus (EBV)-encoded RNA (EBER) is considered the “gold standard” for detecting and localizing latent EBV in biopsy samples. Transcripts from the EBER1 and EBER2 genes are an appropriate target because they are the most abundant viral RNA in latently infected cells, exceeding 1 million transcripts per cell. Furthermore, EBERs are consistently expressed in virtually all EB V-infected tumors and in the lymphoid tissues of infectious mononucleosis (1 –5 ). As a result, EBERs represent a naturally amplified target for detecting and localizing latent EBV in histologic samples. The only EBV-related disorder in which EBER is consistently absent is oral hairy leukoplakia, an infection of squamous epithelial cells in which the virus undergoes lytic viral replication rather than latent infection (6 ).