Abstract
Genome editing technology provides new possibilities for animal breeding and aid in understanding host-pathogen interactions. In poultry, retroviruses display one of the most difficult pathogens to control by conventional strategies such as vaccinations. Avian leukosis virus subgroup J (ALV-J) is an oncogenic, immunosuppressive retrovirus that causes myeloid leukosis and other tumors in chickens. Severe economic losses caused by ALV-J remain an unsolved problem in many parts of the world due to inefficient eradication strategies and lack of effective vaccines. ALV-J attachment and entry are mediated through the specific receptor, chicken Na+/H+ exchanger type 1 (chNHE1). The non-conserved amino acid tryptophan 38 (W38) in chNHE1 is crucial for virus entry, making it a favorable target for the introduction of disease resistance. In this study, we obtained ALV-J-resistance in a commercial chicken line by precise deletion of chNHE1 W38, utilizing the CRISPR/Cas9-system in combination with homology directed repair. The genetic modification completely protected cells from infection with a subgroup J retrovirus. W38 deletion did neither have a negative effect on the development nor on the general health condition of the gene edited chickens. Overall, the generation of ALV-J-resistant birds by precise gene editing demonstrates the immense potential of this approach as an alternative disease control strategy in poultry.
Highlights
During the last decades, poultry industry has grown substantially causing difficulties in disease control
Even though strict eradication programs, similar to those applied for ALVA and B, were able to partially control Avian leukosis virus subgroup J (ALV-J) spread in chickens, subgroup J-related outbreaks are still affecting animal welfare and remain a major threat to poultry industry (Payne and Nair, 2012)
Our findings demonstrate that cells from NHE1 W38−/− transgenic chicken are completely resistant to Avian leukosis virus (ALV)-J infection
Summary
Poultry industry has grown substantially causing difficulties in disease control. Retroviral pathogens continue to be a major problem worldwide Their relatively high antigenic variability (Kurstak et al, 2013) results in the emergence of new strains and interferes with vaccination-based control strategies (Feng and Zhang, 2016). Structural variations of the viral envelope protein underline the evolutionary dynamics responsible for the emergence of new virus strains (Venugopal, 1999). This was illustrated by the identification of ALV-J in the late 80s (Payne, 1998), which increased the number of ALVs that infect chickens to 6 subgroups (ALV A-E and J) (Weiss, 1993). In different Asian countries including China, ALV-J is endemic (Feng and Zhang, 2016), and continues to expand the host range and even includes layer-type chickens (Shen et al, 2014); this expanded host range was shown to be associated with increased pathogenicity (Payne and Nair, 2012)
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