A mammalian fibroblast zoo reveals barriers to cross-species virus replication and differential regulation of antiviral immunity
- 1University of Minnesota
Abstract
Virus zoonosis represents a continual threat to humans. Viruses emerge in humans directly or indirectly through interactions with mammals. However, our understanding of virus-host susceptibility across the diversity of mammals is limited and experimental model systems are restricted to a very small set of model organisms. Mammals are highly diverse and different habitats, lifestyles, diets, and exposures to different pathogens have driven substantial genetic diversity. We generated a library of primary fibroblasts across 86 mammalian species and used these cells to build an atlas of virus-host susceptibility across a panel of arboviruses that infect diverse mammals including humans. Perturbing the innate immune system revealed some virus-host pairs where restriction is controlled by the immune system and others where there is an incompatibility with host factors. Transcriptomic profiling of the library in response to virus sensing mimicked by poly(I:C) or antiviral signaling with type I interferon reveals a core set of conserved genes that respond as well as substantial species- and order-specific responses. Together these data provide a comparative atlas of innate immune responses across mammals and offer a window into how these systems have evolved across animals.
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BibTeX
@misc{mickelson2026mammalian,
title = {{A mammalian fibroblast zoo reveals barriers to cross-species virus replication and differential regulation of antiviral immunity}},
author = {C. K. Mickelson and M. Salnikov and F. K. Shepherd and L. M. Pross and G. McClain and S. Mainali Pokharel and H. H. Hoffmann and T. Schoon and G. Pulinkala and N. Pamornchainavakul and K. Hoffman and C. A. McDonald and E. Vogt and T. T. Neal and A. J. Gilbertsen and D. S. Putri and J. T. Becker and M. J. Pierson and Y. Li and M. T. Aliota and K. H. Dinnon and S. Zec and S. Garity and A. Rivas and J. Rasmussen and A. Wuenschmann and M. Gale and C. M. Rice and J. Komorowski and S. Cherry and R. A. Langlois},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.04.763981},
url = {https://www.biorxiv.org/content/10.64898/2026.11.04.763981v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A mammalian fibroblast zoo reveals barriers to cross-species virus replication and differential regulation of antiviral immunity
AU - C. K. Mickelson
AU - M. Salnikov
AU - F. K. Shepherd
AU - L. M. Pross
AU - G. McClain
AU - S. Mainali Pokharel
AU - H. H. Hoffmann
AU - T. Schoon
AU - G. Pulinkala
AU - N. Pamornchainavakul
AU - K. Hoffman
AU - C. A. McDonald
AU - E. Vogt
AU - T. T. Neal
AU - A. J. Gilbertsen
AU - D. S. Putri
AU - J. T. Becker
AU - M. J. Pierson
AU - Y. Li
AU - M. T. Aliota
AU - K. H. Dinnon
AU - S. Zec
AU - S. Garity
AU - A. Rivas
AU - J. Rasmussen
AU - A. Wuenschmann
AU - M. Gale
AU - C. M. Rice
AU - J. Komorowski
AU - S. Cherry
AU - R. A. Langlois
PY - 2026
DA - 2026/11/04
PB - bioRxiv
DO - 10.64898/2026.11.04.763981
UR - https://www.biorxiv.org/content/10.64898/2026.11.04.763981v1
AB - Virus zoonosis represents a continual threat to humans. Viruses emerge in humans directly or indirectly through interactions with mammals. However, our understanding of virus-host susceptibility across the diversity of mammals is limited and experimental model systems are restricted to a very small set of model organisms. Mammals are highly diverse and different habitats, lifestyles, diets, and exposures to different pathogens have driven substantial genetic diversity. We generated a library of primary fibroblasts across 86 mammalian species and used these cells to build an atlas of virus-host susceptibility across a panel of arboviruses that infect diverse mammals including humans. Perturbing the innate immune system revealed some virus-host pairs where restriction is controlled by the immune system and others where there is an incompatibility with host factors. Transcriptomic profiling of the library in response to virus sensing mimicked by poly(I:C) or antiviral signaling with type I interferon reveals a core set of conserved genes that respond as well as substantial species- and order-specific responses. Together these data provide a comparative atlas of innate immune responses across mammals and offer a window into how these systems have evolved across animals.
ER -