The use of gene editing in cattle has resulted in bovine viral diarrhea (BVDV) resistance. This study, undertaken by USDA researchers and the University of Nebraska, intended to lower a calf’s vulnerability to BVDV. BVDV is a difficult cow illness that harms animal health by weakening the gastrointestinal tract, respiratory system, and reproductive function. It may also be a quiet plague, since sick animals can transfer it to their herd members while seeming healthy.
The researchers employed CRISPR/Cas9 gene editing technology to modify six amino acids in the CD46 gene, which is the site inside the cell where the virus cleaves and enters to infect and multiply in a new host animal. They utilized cloned Gir cow embryos and transferred modified cells to part of them, leaving the other half unedited and serving as “wild-type” controls. Eight embryos of each variety were transplanted into cows.
Of the resulting fetuses, one edited and one unedited fetus were collected at 100 days to assess BVDV resistance in cells from many bodily systems. Ultimately, one full-term pregnancy emerged from an altered embryo, and the calf was delivered by cesarean section at 285 days gestation.
The research discovered that the altered calf was considerably less susceptible to BVDV in a laboratory environment than the unedited fetus. Live tissue samples revealed that the altered calf had a much lower BVDV susceptibility in the three cell types studied – skin fibroblasts, lymphocytes, and monocytes – than the unedited control calf.
The research also found that although gene editing did not completely protect the calf from BVDV, it did greatly increase its capacity to tolerate the viral onslaught. The commercial use of such technology has yet to emerge, but the capacity to help cattle fight BVDV has potentially far-reaching consequences.
Bovine viral diarrhea virus (BVDV) is one of the most burdensome viruses affecting the health and well-being of cattle throughout the world. The main host receptor mediating BVDV infection is CD46. This proof-of-concept study showed that substituting six amino acids in CD46 caused a dramatic reduction in BVDV susceptibility in a gene-edited calf without causing any obvious adverse effects in the first 20 months of life. This provides the first example of gene editing in cattle to reduce the impact of a major viral disease. This approach could significantly improve animal welfare, increase the long-term sustainability of cattle production, and provide an opportunity to reduce antibiotic use in agriculture, given that BVDV infection puts calves at risk for secondary bacterial diseases.
