Mechanistic Insights into Chemoresistance Mediated by Oncogenic Viruses in Lymphomas

Viral lymphomagenesis induced by infection with oncogenic viruses, such as Kaposi's sarcoma associated herpesvirus (KSHV), Epstein-Barr virus (EBV) and human T-cell leukemia virus (HTLV-1), represents a group of aggressive malignancies with a diverse range of pathological features. Combined chemotherapy remains the standard of care for these virus-associated lymphomas; however, frequent chemoresistance is a barrier to achieving successful long-term disease-free survival. There is increasing evidence that indicates virus-associated lymphomas display more resistance to cytotoxic chemotherapeutic agents than that observed in solid tumors. Although the tumor microenvironment and genetic changes, such as key oncogene mutations, are closely related to chemoresistance, some studies demonstrate that the components of oncogenic viruses themselves play pivotal roles in the multidrug chemoresistance of lymphoma cells. In this review, we summarize recent advances in the understanding of the mechanisms through which oncogenic viruses mediate lymphoma cell chemoresistance, with a particular focus on KSHV and EBV, two major oncogenic viruses. We also discuss the current challenges to overcome these obstacles in the treatment of virus-associated lymphomas.