A Genetically Engineered Commercial Chicken Line Is Resistant to Highly Pathogenic Avian Leukosis Virus Subgroup J

Kheimar, Ahmed; Klinger, Romina; Bertzbach, Luca D.; Sid, Hicham; You, Yu; Conradie, Andelé M.; Schade, Benjamin; Böhm, Brigitte; Preisinger, Rudolf; Nair, Venugopal; Kaufer, Benedikt B.; Schusser, Benjamin

doi:10.3390/microorganisms9051066

Cited by 12 publications

(10 citation statements)

References 31 publications

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“…Another problem in veterinary medicine is the avian leukaemia virus. In this Special Issue, Kheimar et al [ 8 ] showed that a genetically engineered chicken with original mutation of ALV-J receptor is resistant to Highly Pathogenic Avian Leukosis Virus Subgroup J, which can be useful for controlling this pathogen and improving poultry health in field conditions.…”

Section: Results and Progressmentioning

confidence: 99%

Avian Pathogens: Editorial and the Perspectives of Research

Sharshov

2022

Microorganisms

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In the last ten years, humanity has faced new challenges in the field of human and animal health, including emerging viral infections. The widespread occurrence of emerging and re-emerging pathogens (e.g., highly pathogenic avian influenza virus (HPAIV), the new COVID-2019 of zoonotic nature, coronaviruses that cause severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS)) presents a serious threat to humans. Avian pathogens cause devastating economic losses in poultry industries worldwide. Poultry is one of the main sources of protein in Asia. For instance, in China alone, with a population of more than 1.3 billion people, poultry meat consumption has increased to 19.6 kg/year per person (FAO). According to official estimates, this is over 25 million tons per year, or more than 12.7 billion birds. Therefore, poultry farming in Southeast Asia is considered one of the main “vessels” where avian pathogens can evolve. Wild bird migration makes the spread of these pathogens to other regions increasingly likely, as we have seen worldwide with the H5N8 influenza virus. In addition, avian pathogens can cause devastating epizootics among wild birds and threaten the planet’s bioresources. The importance of wild birds as potential vectors of disease has received recent renewed interest, especially in the frame of the global virome/microbiome concept. Understanding the spread of bacterial and viral pathogens in wild birds may serve as a useful model for examining the spread of other disease organisms, both among birds, and from birds to other taxa. This Special Issue aims to summarize recent advances and to attract new research articles that address existing pathogens in poultry and wild birds. It also aims to compare the epidemiological situation across avian pathogens or countries.

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Section: Results and Progressmentioning

confidence: 99%

Avian Pathogens: Editorial and the Perspectives of Research

Sharshov

2022

Microorganisms

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“…In this study, we demonstrated that homozygous in vivo knock-out of the chicken tva gene by a frame-shifting deletion in the second exon results in complete resistance to two ALV subgroups, A and K, which share Tva as an entry receptor. After ALV-J, where the complete resistance was achieved by gene editing of the chicken Na + /H + exchanger 1 [30,34], it is the second example of artificial anti-viral resistance conferred by genetic manipulation of the chicken. In pigs, this strategy was employed for resistance to the porcine reproductive and respiratory syndrome virus and transmissible gastroenteritis virus by editing specific receptors CD136 [35] and pAPN [36].…”

Section: Discussionmentioning

confidence: 99%

Knock-Out of Retrovirus Receptor Gene Tva in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B12)-Dependent Level of Methylmalonic Acid

Koslová

Trefil

Mucksová

et al. 2021

Viruses

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The chicken Tva cell surface protein, a member of the low-density lipoprotein receptor family, has been identified as an entry receptor for avian leukosis virus of classic subgroup A and newly emerging subgroup K. Because both viruses represent an important concern for the poultry industry, we introduced a frame-shifting deletion into the chicken tva locus with the aim of knocking-out Tva expression and creating a virus-resistant chicken line. The tva knock-out was prepared by CRISPR/Cas9 gene editing in chicken primordial germ cells and orthotopic transplantation of edited cells into the testes of sterilized recipient roosters. The resulting tva −/− chickens tested fully resistant to avian leukosis virus subgroups A and K, both in in vitro and in vivo assays, in contrast to their susceptible tva +/+ and tva +/− siblings. We also found a specific disorder of the cobalamin/vitamin B12 metabolism in the tva knock-out chickens, which is in accordance with the recently recognized physiological function of Tva as a receptor for cobalamin in complex with transcobalamin transporter. Last but not least, we bring a new example of the de novo resistance created by CRISPR/Cas9 editing of pathogen dependence genes in farm animals and, furthermore, a new example of gene editing in chicken.

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“…In summary, we have identified a novel ISG, ACSL1, that is important to inhibit ALV-J replication. Inhibition of virus replication in a host population can significantly reduce the change of viral adaption (44). The availability of genome-editing tools, notably CRISPR/Cas9, widens the scope of animal breeding and its applications in the context of disease control, while targeted genome editing has been proven useful to resistant ALV-J in chickens (34,44,45).…”

Section: Discussionmentioning

confidence: 99%

“…Inhibition of virus replication in a host population can significantly reduce the change of viral adaption (44). The availability of genome-editing tools, notably CRISPR/Cas9, widens the scope of animal breeding and its applications in the context of disease control, while targeted genome editing has been proven useful to resistant ALV-J in chickens (34,44,45). In this context, exploiting more antiviral genes are particularly valuable in chickens.…”

Section: Discussionmentioning

confidence: 99%

ACSL1 Inhibits ALV-J Replication by IFN-Ⅰ Signaling and PI3K/Akt Pathway

Zhang

Xie

et al. 2021

Front. Immunol.

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J subgroup avian leukosis virus (ALV-J) infection causes serious immunosuppression problems, leading to hematopoietic malignancy tumors in chicken. It has been demonstrated that interferon-stimulated genes (ISGs) could limit ALV-J replication; nevertheless, the underlying mechanisms remain obscure. Here, we demonstrate that Long-chain Acyl-CoA synthetase 1 (ACSL1) is an interferon (IFN)-stimulated gene that specifically restricts the replication of ALV-J due to the higher IFN-I production. More importantly, ACSL1 induces primary monocyte-derived macrophages (MDMs) to pro-inflammatory phenotypic states during ALV-J infection, and ACSL1 mediates apoptosis through the PI3K/Akt signaling pathway in ALV-J-infected primary monocyte-derived macrophages (MDMs). Overall, these results provide evidence that ACSL1 contributes to the antiviral response against ALV-J.

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A Genetically Engineered Commercial Chicken Line Is Resistant to Highly Pathogenic Avian Leukosis Virus Subgroup J

Cited by 12 publications

References 31 publications

Avian Pathogens: Editorial and the Perspectives of Research

Avian Pathogens: Editorial and the Perspectives of Research

Knock-Out of Retrovirus Receptor Gene Tva in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B12)-Dependent Level of Methylmalonic Acid

ACSL1 Inhibits ALV-J Replication by IFN-Ⅰ Signaling and PI3K/Akt Pathway

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