Biology subjects

Eitson, J. L.

Publications and source records attributed to Eitson, J. L..

3 recordsLinked to original sources

bioRxiv2024

IRF7 from the black flying fox induces a STAT1-independent ISG response in unstimulated cell lines that protects against diverse RNA viruses

Bats are considered unique in their ability to harbor large numbers of viruses and serve as reservoirs for zoonotic viruses that have the potential to spill over into humans. However, these animals appear relatively resistant to the pathogenic effects of many viruses. Mounting evidence suggests that bats may tolerate viral infections due to unique immune features. These include evolutionary innovations in inflammatory pathways and in the molecules involved in viral sensing, interferon induction, and downstream interferon-induced antiviral effectors. We sought to determine whether interferon-stimulated genes (ISGs) from the black flying fox (Pteropus alecto) encoded proteins with unique antiviral activity relative to their human orthologs. Accordingly, we compared the antiviral activity of over 50 ISG human-bat ortholog pairs to identify differences in individual effector functions. We identified IRF7 from Pteropus alecto (Pa.IRF7) as a potent and broad-acting antiviral molecule that provides robust antiviral protection without prior activation. We show that Pa.IRF7 uniquely induces a subset of protective ISGs independent of canonical IFN signaling, which leads to protection from alphaviruses, a flavivirus, a rhabdovirus, and a paramyxovirus. In uninfected cells, Pa.IRF7 partially localizes to the nucleus and can directly bind interferon-sensitive regulatory elements (ISREs). Compared to human IRF7, Pa.IRF7 also has additional serines in its C terminal domain that contribute to antiviral activity and may serve as unique phosphorylation hubs for activation. These properties constitute major differences between bat and human IRF7 that offer additional insight into the potential uniqueness of the black flying fox immune system.

immunology↗

bioRxiv2023

LY6E protects mice from pathogenic effects of murine coronavirus and SARS-CoV-2

LY6E is an antiviral protein that inhibits coronavirus entry. Its expression in immune cells allows mice to control murine coronavirus infection. However, it is not known which immune cell subsets mediate this control or whether LY6E protects mice from SARS-CoV-2. In this study, we used tissue-specific Cre recombinase expression to ablate Ly6e in distinct immune compartments or in all epiblast-derived cells, and bone marrow chimeras to target Ly6e in a subset of radioresistant cells. Mice lacking Ly6e in Lyz2-expressing cells and radioresistant Vav1-expressing cells were more susceptible to lethal murine coronavirus infection. Mice lacking Ly6e globally developed clinical disease when challenged with the Gamma (P.1) variant of SARS-CoV-2. By contrast, wildtype mice and mice lacking type I and type III interferon signaling had no clinical symptoms after SARS-CoV-2 infection. Transcriptomic profiling of lungs from SARS-CoV-2-infected wildtype and Ly6e knockout mice revealed a striking reduction of secretory cell-associated genes in infected knockout mice, including Muc5b, an airway mucin-encoding gene that may protect against SARS-CoV-2-inflicted respiratory disease. Collectively, our study reveals distinct cellular compartments in which Ly6e confers cell intrinsic antiviral effects, thereby conferring resistance to disease caused by murine coronavirus and SARS-CoV-2.

microbiology↗

bioRxiv2022

Genome-scale CRISPR screening reveals host factors required for ribosome formation and viral replication

Viruses are known to co-opt host machinery for translation initiation, but less is known about which host factors are required for the formation of ribosomes used to synthesize viral proteins. Using a loss of function CRISPR screen, we show that synthesis of a flavivirus encoded reporter depends on multiple host factors, including several 60S ribosome biogenesis proteins. Viral phenotyping revealed that two of these factors, SBDS, a known ribosome biogenesis factor, and the relatively uncharacterized protein SPATA5, were broadly required for replication of flaviviruses, coronaviruses, alphaviruses, paramyxoviruses, an enterovirus, and a poxvirus. Mechanistic studies revealed that loss of SPATA5 caused defects in ribosomal RNA processing and ribosome assembly, suggesting that this human protein may be a functional ortholog of yeast Drg1. These studies implicate specific ribosome biogenesis proteins as viral host dependency factors that are required for synthesis of virally encoded protein and accordingly, optimal viral replication.

microbiology↗