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 Trivett, Douwe M. T. Bosma, Julia Rühl, Norbert Goebels, Denise Whitby and Christian Münz ()
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Nicole Caduff: University of Zürich
Lisa Rieble: University of Zürich
Michelle Böni: University of Zürich
Donal McHugh: University of Zürich
Romin Roshan: Frederick National Laboratory for Cancer Research
Wendell Miley: Frederick National Laboratory for Cancer Research
Nazzarena Labo: Frederick National Laboratory for Cancer Research
Sumanta Barman: Heinrich Heine University Düsseldorf
Matthew Trivett: Frederick National Laboratory for Cancer Research
Douwe M. T. Bosma: University of Zürich
Julia Rühl: University of Zürich
Norbert Goebels: Heinrich Heine University Düsseldorf
Denise Whitby: Frederick National Laboratory for Cancer Research
Christian Münz: University of Zürich

Nature Communications, 2024, vol. 15, issue 1, 1-13

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.

Date: 2024
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DOI: 10.1038/s41467-024-49209-w

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