Abstract

Epstein-Barr virus (EBV) infects more than 90% of adults worldwide and causes a range of diseases, including multiple malignancies and autoimmune disorders. However, due to a host range restriction, EBV cannot infect commonly used experimental animals, posing a significant obstacle to developing EBV-specific prophylactic and therapeutic agents. Rhesus lymphocryptovirus (rhLCV), an ortholog of EBV, naturally infects rhesus macaques, which is a surrogate model for EBV research. In this study, we demonstrate that cynomolgus macaque (Macaca fascicularis), a primate closely related to rhesus macaque, is susceptible to rhLCV infection. rhLCV can immortalize B cells of cynomolgus macaques to develop cy-LCLs. We developed a high rhLCV-producing cy-LCL cell line, LCL111, and optimized the induction conditions to increase viral production, surpassing the original rhLCV producer LCL8664. Importantly, EBV gHgL-specific monoclonal antibody (mAb) AMMO1 and gB-specific mAb 3A5 can cross-react with rhLCV proteins and block the formation of cy-LCLs. Overall, we established an efficient rhLCV-producing cell line, and rhLCV infection of cynomolgus macaques represents a promising alternative surrogate model for efficiency evaluation of EBV vaccines and mAbs.