Abstract
Viral diseases remain a major concern for animal health and global food production in modern agriculture. In chickens, avian leukosis virus subgroup J (ALV-J) represents an important pathogen that causes severe economic loss. Until now, no vaccine or antiviral drugs are available against ALV-J and strategies to combat this pathogen in commercial flocks are desperately needed. CRISPR/Cas9 targeted genome editing recently facilitated the generation of genetically modified chickens with a mutation of the chicken ALV-J receptor Na+/H+ exchanger type 1 (chNHE1). In this study, we provide evidence that this mutation protects a commercial chicken line (NHE1ΔW38) against the virulent ALV-J prototype strain HPRS-103. We demonstrate that replication of HPRS-103 is severely impaired in NHE1ΔW38 birds and that ALV-J-specific antigen is not detected in cloacal swabs at later time points. Consistently, infected NHE1ΔW38 chickens gained more weight compared to their non-transgenic counterparts (NHE1W38). Histopathology revealed that NHE1W38 chickens developed ALV-J typical pathology in various organs, while no pathological lesions were detected in NHE1ΔW38 chickens. Taken together, our data revealed that this mutation can render a commercial chicken line resistant to highly pathogenic ALV-J infection, which could aid in fighting this pathogen and improve animal health in the field.
Highlights
All chickens were kept in the same room to assess whether NHE1∆W38 are protected against Avian leukosis viruses (ALVs) subgroup J (ALV-J) even in a virus-contaminated environment
To assess virus replication in the infected animals, blood was collected at 7, 14, 21, 28, 35, 49, 63, and 77 dpi and ALV-J proviral genome copies determined by quantitative PCR (qPCR)
Constant shedding of ALV-specific p27 was observed in NHE1W38 birds, while no shedding was observed in NHE1∆W38 birds (Figure 1B)
Summary
Avian leukosis viruses (ALVs) are common retroviruses in domestic chickens associated with neoplasia and immunosuppression [1]. ALVs comprise ten distinct subgroups including ALV subgroup J (ALV-J) which currently represents the most prevalent in the field [2]. ALV-J infections often progress subclinical and lead to a severe reduction in egg and meat production [3,4]. Myeloid leukosis (ML), the primary neoplastic disorder induced by subgroup J, is characterized by various tumor types with a high incidence of renal tumors and gross skeletal myelocytomas [1,5]
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