KSHV infection of B cells primes protective T cell responses in humanized mice
Nicole Caduff, Lisa Rieble, Michelle Böni, Donal McHugh, Romin Roshan, Wendell Miley, Nazzarena Labo, Sumanta Barman, Matthew T. Trivett, Douwe M. T. Bosma, Julia Rühl, Norbert Goebels, Denise Whitby, Christian Münz
Abstract
Abstract Kaposi sarcoma associated herpesvirus (KSHV) is associated with around 1% of all human tumors, including the B cell malignancy primary effusion lymphoma (PEL), in which co-infection with the Epstein Barr virus (EBV) can almost always be found in malignant cells. Here, we demonstrate that KSHV/EBV co-infection of mice with reconstituted human immune systems (humanized mice) leads to IgM responses against both latent and lytic KSHV antigens, and expansion of central and effector memory CD4 + and CD8 + T cells. Among these, KSHV/EBV dual-infection allows for the priming of CD8 + T cells that are specific for the lytic KSHV antigen K6 and able to kill KSHV/EBV infected B cells. This suggests that K6 may represent a vaccine antigen for the control of KSHV and its associated pathologies in high seroprevalence regions, such as Sub-Saharan Africa.