Immunological features of bats: resistance and tolerance to emerging viruses

Demian, Wael L.; Cormier, Olga; Mossman, Karen

doi:10.1016/j.it.2024.01.008

Cited by 2 publications

(1 citation statement)

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“…With respect to mechanisms that may allow viruses to tolerate infection, certain bat species have been shown to have a functionally impaired NLRP3 inflammasomes or a complete loss of inflammatory PHYIN genes (Ahn et al, 2019; Ahn et al, 2016). With respect to antiviral pathways, relative to humans, some bats have greater numbers of IFN genes, while other bats have a contracted IFN gene repertoire (Demian et al, 2024). The biological relevance of IFN gene numbers in bats, or any other IFN-expressing vertebrate, is not known.…”

Section: Introductionmentioning

confidence: 99%

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

Cruz-Rivera,

Eitson,

Schoggins

2024

Preprint

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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.

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Section: Introductionmentioning

confidence: 99%