Antiviral effects of interferon-stimulated genes in bats

Zhang, Dan; Irving, Aaron T.

doi:10.3389/fcimb.2023.1224532

Cited by 5 publications

(2 citation statements)

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“…Screening the virome for over 4000 healthy bats from 40 different species of both Yangochiroptera and Yinpterochiroptera suborders, revealed an array of viruses belonging to diverse families, the most prevalent being Herpesviridae, Papillomaviridae, Retroviridae, Adenoviridae and Astroviridae, but also Coronaviridae, Caliciviridae, Polyomaviridae, Rhabdoviridae, among others ( 33 ), confirming bats as reservoirs of various virus. The unique ability of bats to act as reservoirs is thought to be mediated by a dampening of pro-inflammatory responses ( 30 , 32 , 34 ) as well as an increased resistance to infection mediated by special features of the antiviral type I interferon (IFN) system [reviewed in ( 35 )]. GBP s are IFN-induced GTPases that have been shown to have vital roles in host immunity to infection and inflammation.…”

Section: Discussionmentioning

confidence: 99%

Evolution of guanylate binding protein genes shows a remarkable variability within bats (Chiroptera)

Pinheiro,

Borges,

Côrte-Real

et al. 2024

Front. Immunol.

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BackgroundGBPs (guanylate binding proteins), an evolutionary ancient protein family, play a key role in the host’s innate immune response against bacterial, parasitic and viral infections. In Humans, seven GBP genes have been described (GBP1-7). Despite the interest these proteins have received over the last years, evolutionary studies have only been performed in primates, Tupaia and rodents. These have shown a pattern of gene gain and loss in each family, indicative of the birth-and-death evolution process.ResultsIn this study, we analysed the evolution of this gene cluster in several bat species, belonging to the Yangochiroptera and Yinpterochiroptera sub-orders. Detailed analysis shows a conserved synteny and a gene expansion and loss history. Phylogenetic analysis showed that bats have GBPs 1,2 and 4-6. GBP2 has been lost in several bat families, being present only in Hipposideidae and Pteropodidae. GBPs1, 4 and 5 are present mostly as single-copy genes in all families but have suffered duplication events, particularly in Myotis myotis and Eptesicus fuscus. Most interestingly, we demonstrate that GBP6 duplicated in a Chiroptera ancestor species originating two genes, which we named GBP6a and GBP6b, with different subsequent evolutionary histories. GBP6a underwent several duplication events in all families while GBP6b is present as a single copy gene and has been lost in Pteropodidae, Miniopteridae and Desmodus rotundus, a Phyllostomidae. With 14 and 15 GBP genes, Myotis myotis and Eptesicus fuscus stand out as having far more copies than all other studied bat species. Antagonistically, Pteropodidae have the lowest number of GBP genes in bats.ConclusionBats are important reservoirs of viruses, many of which have become zoonotic diseases in the last decades. Further functional studies on bats GBPs will help elucidate their function, evolutionary history, and the role of bats as virus reservoirs.

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Section: Discussionmentioning

confidence: 99%

Evolution of guanylate binding protein genes shows a remarkable variability within bats (Chiroptera)

Pinheiro,

Borges,

Côrte-Real

et al. 2024

Front. Immunol.

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“…Host and viruses need to constantly evolve to gain a survival advantage over each other, viruses therefore impose strong selection pressures on the host immune system (Brockhurst et al, 2014). In fact, several non-human ISGs have been shown to have differential functional capacity compared to their human counterparts (Zhang & Irving, 2023). ISGs also have a higher rate of gene duplication compared to other genes which may enhance their potency and diversity (Shaw et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Alternative splicing expands the antiviral IFITM repertoire in Chinese horseshoe bats

Mak,

Zhang,

et al. 2023

Preprint

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The interferon response is shaped by the evolutionary arms race between hosts and the pathogens they carry. The human interferon-induced transmembrane protein (IFITM) family consists of three antiviralIFITMgenes that arose by gene duplication, they restrict virus entry and are key players of the interferon response. Yet, little is known about IFITMs in other mammals. Here, we identified anIFITMgene in Chinese horseshoe bat, a natural host of SARS-coronaviruses, that is alternatively spliced to produce two IFITM isoforms. These bat IFITMs have conserved structures in vitro and differential antiviral activities against influenza A virus and coronaviruses including SARS- and MERS-coronavirus. In parallel with human IFITM1-3, the bat IFITM isoforms localize to distinct cellular compartments. Further analysis of IFITM repertoires in 205 mammals reveals that alternative splicing is a ubiquitous strategy for IFITM diversification, albeit less widely adopted than gene duplication. These findings showcase an example of convergent evolution where species-specific selection pressures led to expansion of the IFITM family through multiple means, underscoring the importance of IFITM diversity as a component of innate immunity.

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