Biology subjects

Pross, L. M.

Publications and source records attributed to Pross, L. M..

2 recordsLinked to original sources

bioRxiv2026

A mammalian fibroblast zoo reveals barriers to cross-species virus replication and differential regulation of antiviral immunity

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.

immunology↗

bioRxiv2024

Mammalian ZAP and KHNYN independently restrict CpG-enriched avian viruses

Zoonotic viruses are an omnipresent threat to global health. Influenza A virus (IAV) transmits between birds, livestock, and humans. Proviral host factors involved in the cross-species interface are well known. Less is known about antiviral mechanisms that suppress IAV zoonoses. We observed CpG dinucleotide depletion in human IAV relative to avian IAV. Notably, human ZAP selectively depletes CpG-enriched viral RNAs with its cofactor KHNYN. ZAP is conserved in tetrapods but we uncovered that avian species lack KHNYN. We found that chicken ZAP may not affect IAV (PR8) or CpG enriched IAV (PR8CG). Human ZAP or KHNYN independently restricted CpG-enriched IAV PR8CG by overexpression in chicken cells and by combined knockout in human cells. Additionally, mammalian ZAP-L and KHNYN also independently restricted an avian retrovirus (ROSV). Curiously, platypus KHNYN, the most divergent from eutherian mammals, was also capable of independent restriction of multiple diverse viruses. We suggest that some mammalian KHNYN can act as a bona fide restriction factor with cell-autonomous activity. Furthermore, we speculate that through repeated contact between avian viruses and mammalian hosts, protein changes may accompany CpG-biased mutations or reassortment to evade mammalian ZAP and KHNYN.

microbiology↗