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- Title
KSHV infection of B cells primes protective T cell responses in humanized mice.
- Authors
Caduff, Nicole; Rieble, Lisa; Böni, Michelle; McHugh, Donal; Roshan, Romin; Miley, Wendell; Labo, Nazzarena; Barman, Sumanta; Trivett, Matthew; Bosma, Douwe M. T.; Rühl, Julia; Goebels, Norbert; Whitby, Denise; Münz, Christian
- 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. Kaposi sarcoma associated herpesvirus (KSHV) and Epstein Barr virus often co-infect hosts and some malignancies, such as primary effusion lymphoma, are typically arising from dual-infected cells. Here authors recapitulate dual infection in a humanized mouse model, and find that under these conditions, an efficient and specific CD8+ T cell response is mounted against the lytic KSHV antigen K6.
- Subjects
SUB-Saharan Africa; T cells; B cells; B cell lymphoma; CANCER cells; KAPOSI'S sarcoma; MICE; B cell receptors
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-49209-w