Gammaherpesvirus infection of myeloid cells reveals divergent outcomes regulated by host and viral factors
Abstract
The gammaherpesviruses establish a lifelong infection, with the cellular outcome of infection intimately regulated by cell type. Myeloid cells are an early infection target characterized by diverse outcomes. To investigate this, we use murine gammaherpesvirus 68 to demonstrate that macrophages are readily infectable, resulting in three divergent infection outcomes dictated by viral and host factors. Infection in vivo and in a cell culture model results in a high frequency of viable cells characterized by restricted viral transcription and unexpected transcription of the ORF75 locus, with rare cells initiating lytic replication. Restricted infection can be fully converted to productive lytic replication by pre-treatment with the host cytokine interleukin 4 (IL-4). Finally, infection with a high viral dose also results in productive infection, but it triggers increased cell death. These studies demonstrate stepwise regulation of virus infection and identify virus and host factors that dictate divergent outcomes in a single cell type.
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BibTeX
@article{vragel2026gammaherpesvirus,
title = {{Gammaherpesvirus infection of myeloid cells reveals divergent outcomes regulated by host and viral factors}},
author = {Gabrielle Vragel and Kyra S. Noell and Ashley Tseng and Rachael E. Kostelecky and Elizabeth A. Alexander and Shirli Cohen and Catalina Galvan and Manaal Dalwadi and Brittany D. Gomez and Eva M. Medina and Darby G. Oldenburg and Andrew Goodspeed and Eric T. Clambey and Linda F. van Dyk},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117872},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03255-4},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Gammaherpesvirus infection of myeloid cells reveals divergent outcomes regulated by host and viral factors
AU - Gabrielle Vragel
AU - Kyra S. Noell
AU - Ashley Tseng
AU - Rachael E. Kostelecky
AU - Elizabeth A. Alexander
AU - Shirli Cohen
AU - Catalina Galvan
AU - Manaal Dalwadi
AU - Brittany D. Gomez
AU - Eva M. Medina
AU - Darby G. Oldenburg
AU - Andrew Goodspeed
AU - Eric T. Clambey
AU - Linda F. van Dyk
PY - 2026
DA - 2026/10/13
JO - iScience
DO - 10.1016/j.isci.2026.117872
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03255-4
AB - The gammaherpesviruses establish a lifelong infection, with the cellular outcome of infection intimately regulated by cell type. Myeloid cells are an early infection target characterized by diverse outcomes. To investigate this, we use murine gammaherpesvirus 68 to demonstrate that macrophages are readily infectable, resulting in three divergent infection outcomes dictated by viral and host factors. Infection in vivo and in a cell culture model results in a high frequency of viable cells characterized by restricted viral transcription and unexpected transcription of the ORF75 locus, with rare cells initiating lytic replication. Restricted infection can be fully converted to productive lytic replication by pre-treatment with the host cytokine interleukin 4 (IL-4). Finally, infection with a high viral dose also results in productive infection, but it triggers increased cell death. These studies demonstrate stepwise regulation of virus infection and identify virus and host factors that dictate divergent outcomes in a single cell type.
SN - 2589-0042
ER -