Reinstatement of<i>RIG-I</i>in chickens via genetic modification reveals new insights into the dynamic evolution of avian immune sensors

Sid, Hicham; von Heyl, Theresa; Schleibinger, Sabrina; Klinger, Romina; Guabiraba, Rodrigo; Guillory, Vanaique; Schade, Benjamin; Elleder, Daniel; Sives, Samantha; Vervelde, Lonneke; Trapp, Sascha; Schusser, Benjamin

doi:10.1101/2023.11.01.564710

Cited by 3 publications

(2 citation statements)

References 59 publications

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“…Recent advancements in genome editing technology have spearheaded the development of transgenic chickens with the hope of combating AIV infection. Several strategies have been employed to create AIV resistant chickens including, using shorthairpin RNAs to interfere with AIV replication, introducing a specific gene edit to impede ANP32A function, and introducing an innate antiviral signaling transgene (RIG-I) to enhance the innate immune response [44][45][46]. The success of each of these strategies was variable with chickens succumbing to disease, breakthrough infections at high inoculum doses, and/or AIV mutations to overcome host boundaries [44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Genetic insertion of mouse Myxovirus-resistance gene 1 increases innate resistance against both high and low pathogenic avian influenza virus by significantly decreasing replication in chicken DF1 cell line

Briggs,

Chrzastek,

Segovia

et al. 2024

Preprint

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Avian influenza virus (AIV) is a constant threat to animal health with recent global outbreaks resulting in the death of hundreds of millions of birds with spillover into mammals. Myxovirus-resistance (Mx) proteins are key mediators of the antiviral response that block virus replication. Mouse (Mu) Mx (Mx1) is a strong antiviral protein that interacts with the viral nucleoprotein to inhibit polymerase function. The ability of avian Mx1 to inhibit AIV is unclear. In these studies, Mu Mx1 was stably introduced into chicken DF1 cells to enhance the immune response against AIV. Following infection, titers of AIV were significantly decreased in cells expressing Mu Mx1. In addition, considerably less cytopathic effect (CPE) and matrix protein staining was observed in gene-edited cells expressing Mu Mx1, suggesting Mu Mx1 is broadly effective against multiple AIV subtypes. This work provides foundational studies for use of gene-editing to enhance innate disease resistance against AIV.

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Section: Discussionmentioning

confidence: 99%

Genetic insertion of mouse Myxovirus-resistance gene 1 increases innate resistance against both high and low pathogenic avian influenza virus by significantly decreasing replication in chicken DF1 cell line

Briggs,

Chrzastek,

Segovia

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…For example, the chicken is widely used as an amniote model in developmental biology research (Sheng, 2021). Also, the duck, a natural reservoir of avian influenza virus, is an important target species in the areas of avian immunology and zoonotic diseases (Barber et al, 2010: Evseev & Magor, 2019Ichikawa et al, 2021;Sid et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Innovations in poultry reproduction using cryopreserved avian germ cells

Ichikawa,

McGrew

2024

Reprod Domestic Animals

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Meat and eggs from chicken are the major source of animal protein for the human population. The cryopreservation of poultry species is needed to guarantee sustainable production. Here, we describe the existing cryopreservation technologies for avian reproductive cells using embryonic germ cells, spermatozoa and ovarian tissues. We outline strategies to reconstitute chicken breeds from their cryopreserved embryonic germ cells using surrogate hosts and discuss the perspectives for genetic conservation and reconstitution of chicken and wild avian species using surrogate host animals.

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Modelling molecular differences in the innate immune system responses of chickens and ducks to highly pathogenic avian influenza virus

Wood,

An,

Bryant

et al. 2024

Preprint

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Highly pathogenic avian influenza virus (HPAIV) presents a global threat to chicken livestock; chickens infected by HPAIV tend to show severe symptoms and high mortality rates. In 2022, the largest recorded outbreak of HPAIV in Europe resulted in millions of chickens being culled in the UK alone to try to prevent further spread. Unlike chickens, mallard ducks show reduced symptom severity and lower mortality rates to HPAIV infection. Research into the immune system responses of these two species shows they differ in their molecular outputs: chickens produce a pro-inflammatory response; mallards produce an anti-viral response. These differences in immune responses are thought to be in part due to chickens missing pattern recognition receptor retinoic acid-inducible gene-I (RIG-I). This project aimed to model the innate immune systems of chickens and mallard ducks to an abstracted molecular level. A literature search was conducted, and the immune systems were modelled in NetLogo as an avian innate immune response agent-based model (AIIRABM). The AIIRABM enabled examination of the relative importance of molecular differences between the chicken and mallard duck innate immune systems and produced similar differences in chicken and mallard duck molecular outputs to those observed in vitro and in vivo. Simulation experiments with the AIIRABM supported the molecular difference RIG-I as key in causing the differences in the chicken and mallard duck innate immune responses to HPAIV. The AIIRABM will be used in further research on the chicken and mallard duck immune responses to HPAIV as the baseline in an iterative modelling cycle.

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Reinstatement ofRIG-Iin chickens via genetic modification reveals new insights into the dynamic evolution of avian immune sensors

Cited by 3 publications

References 59 publications

Genetic insertion of mouse Myxovirus-resistance gene 1 increases innate resistance against both high and low pathogenic avian influenza virus by significantly decreasing replication in chicken DF1 cell line

Genetic insertion of mouse Myxovirus-resistance gene 1 increases innate resistance against both high and low pathogenic avian influenza virus by significantly decreasing replication in chicken DF1 cell line

Innovations in poultry reproduction using cryopreserved avian germ cells

Modelling molecular differences in the innate immune system responses of chickens and ducks to highly pathogenic avian influenza virus

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