Cytokine signaling regulates multiple stages of gammaherpesvirus infection in myeloid cells
- 1CU Anschutz Medical Campus
Abstract
The gammaherpesviruses, including Epstein-Barr Virus and Kaposis Sarcoma-associated Herpesvirus, establish lifelong infections by maintaining a balance between lytic and latent infection states. How this balance is regulated in myeloid cells, an important but understudied cell type that can achieve both infection states, remains unclear. Using the murine gammaherpesvirus 68 (MHV68) model, we show that IFNg; and IL-4 reciprocally regulate lytic infection in macrophages in a time- and JAK/STAT signaling dependent-manner, with basal JAK/STAT signaling further restricting lytic infection. Using a combination of MHV68 reporter viruses, cellular and molecular techniques, we demonstrate that IFNg blocks lytic replication through at least two distinct mechanisms, restricting delivery to or stability of the viral genome in the nucleus and potently restricting lytic cycle progression downstream of the immediate-early viral transactivator, RTA. These findings define specific points during lytic infection where IFNg; to enforce restricted, latent-like infection in myeloid cells.
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BibTeX
@misc{kostelecky2026cytokine,
title = {{Cytokine signaling regulates multiple stages of gammaherpesvirus infection in myeloid cells}},
author = {R. Kostelecky and G. Vragel and P. Gamez and E. M. Medina and D. Oldenburg and A. Goodspeed and C. Weigel and R. Baiocchi and E. T. Clambey and L. van Dyk},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.749271},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749271v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Cytokine signaling regulates multiple stages of gammaherpesvirus infection in myeloid cells
AU - R. Kostelecky
AU - G. Vragel
AU - P. Gamez
AU - E. M. Medina
AU - D. Oldenburg
AU - A. Goodspeed
AU - C. Weigel
AU - R. Baiocchi
AU - E. T. Clambey
AU - L. van Dyk
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.749271
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.749271v1
AB - The gammaherpesviruses, including Epstein-Barr Virus and Kaposis Sarcoma-associated Herpesvirus, establish lifelong infections by maintaining a balance between lytic and latent infection states. How this balance is regulated in myeloid cells, an important but understudied cell type that can achieve both infection states, remains unclear. Using the murine gammaherpesvirus 68 (MHV68) model, we show that IFNg; and IL-4 reciprocally regulate lytic infection in macrophages in a time- and JAK/STAT signaling dependent-manner, with basal JAK/STAT signaling further restricting lytic infection. Using a combination of MHV68 reporter viruses, cellular and molecular techniques, we demonstrate that IFNg blocks lytic replication through at least two distinct mechanisms, restricting delivery to or stability of the viral genome in the nucleus and potently restricting lytic cycle progression downstream of the immediate-early viral transactivator, RTA. These findings define specific points during lytic infection where IFNg; to enforce restricted, latent-like infection in myeloid cells.
ER -