Abstract
Epstein-Barr virus (EBV), a member of the herpesvirus family, infects more than 90% of
adults and establishes a lifelong latent infection. In addition to its involvement in a wide range of
malignancies such as lymphomas, nasopharyngeal carcinoma, and gastric cancer, recent evidence
has shown its potential association with autoimmune diseases, positioning EBV as an
interdisciplinary research model linking virology, oncology, and immunology. Historically, EBV
research has been hindered by technical limitations in viral culture systems and animal models.
However, recent advances—including whole-genome cloning using bacterial artificial chromosomes
(BACs), gene editing via CRISPR/Cas9, and the development of in vivo models such as humanized
mice—have accelerated the elucidation of EBV’ s unique life cycle and tumorigenic mechanisms. In
this review, we discuss the evolution of techniques for generating recombinant EBVs and in vivo
modeling, both essential for functional genetic analysis, and highlight our contributions to the
advancement of these tools and their application in researching EBV-associated tumorigenesis.
