KSHV vIL6 Inhibits Functional B Cell Maturation During De Novo Infection

Authors

Wajd Zakir, Chapman UniversityFollow
Jessica M. Osborn, Oregon Health and Science University
Jennifer Totonchy, Chapman UniversityFollow

Document Type

Article

Publication Date

7-7-2025

Abstract

Despite causative links to lymphoproliferative disorders, little is known about early events governing KSHV infection in B lymphocytes. IL-6 signaling plays a critical role in KSHV-mediated disease, with human IL-6 (hIL6) levels correlating with viral load and disease progression. This dynamic is even more complex due to the coexistence of hIL6 and KSHV-encoded viral IL-6 (vIL6) in these diseases. We hypothesize that hIL6 and vIL6 play critical, separable and collective roles in the early stages of KSHV infection in B cells. In this study, we use our ex vivo model of KSHV infection in human tonsil lymphocytes to investigate the relative contributions of vIL6 and hIL6 to early infection events in human B cells. We demonstrate that vIL6 and hIL6 collectively suppress KSHV infection in B cells restricting the distribution of KSHV within B cell subsets. We show that vIL6 manipulates hIL6 expression in a subset-specific manner, and that vIL6 and hIL6 differentially influence the differentiation of germinal center and plasmablasts. Taken together, these results suggest a novel paradigm in which KSHV uses vIL6 to abrogate the GC-mediated maturation pathway for antibody secreting cells that is driven by hIL6 signaling.

Comments

This article was originally published in Journal of Medical Virology, volume 97, issue 7, in 2025. https://doi.org10.1002/jmv.70479

Recommended Citation

Zakir W, Osborn JM, Totonchy JE. KSHV vIL6 Inhibits Functional B Cell Maturation During De Novo Infection. J Med Virol. 2025;97(7):e70479. https://doi.org10.1002/jmv.70479

Copyright

The authors

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License