Categories: Immune system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 107310 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2020

Species-specific description: Chai and Bates (2006) identified the receptor for subgroup J viruses as being the Na+/H+ exchanger type 1 (chNHE1).

Molecular basis: Using "precise CRISPR/Cas9 gene editing", Koslová et al. (2020) deleted the triplet for the critical receptor amino acid (W38) in the chNHE1 gene that encodes functional receptor for subgroup J leukosis virus, creating ΔW38. The authors reported that "The resistance to ALV-J was examined both in vitro and in vivo, and the ΔW38 homozygous chickens tested ALV-J-resistant, in contrast to ΔW38 heterozygotes and wild-type birds, which were ALV-J-susceptible. Deletion of W38 did not manifest any visible side effect."
Matoušková et al. (2024) "To investigate the capacity of ALV-J for further adaptation, we used a retrovirus reporter-based assay to select adapted ALV-J variants. ... [The authors] isolated and sequenced numerous adapted virus variants and found within their envelope genes eight independent single nucleotide substitutions. To confirm the adaptive capacity of these substitutions, [the aughors] introduced them into the original retrovirus reporter. All eight variants replicated effectively in W38-/- chicken embryonic fibroblasts in vitro while in vivo, W38-/- chickens were sensitive to tumor induction by two of the variants. Importantly, receptor alleles with more extensive modifications have remained resistant to the virus. These results demonstrate an important strategy in livestock genome engineering towards antivirus resistance and illustrate that cellular resistance induced by minor receptor modifications can be overcome by adapted virus variants."

Associated gene: