Gene-edited Calf May Reduce Reliance on Antimicrobials Against Cattle Disease

Cattle worldwide face major health threats from a highly infectious viral disease that decades of vaccinations and other precautions have failed to contain. Federal, private-sector and University of Nebraska-Lincoln scientists are collaborating on a new line of defense, by producing a gene-edited calf resistant to the virus.

If follow-up research confirms its efficacy, the gene-editing approach offers long-term potential to reduce antimicrobial and antibiotic use in the cattle industry.

The bovine viral diarrhea virus (BVDV) devastates the bovine immune system and can cause severe respiratory and intestinal harm to infected beef and dairy cattle, said veterinary epidemiologist Brian Vander Ley, an associate professor in the University of Nebraska-Lincoln's School of Veterinary Medicine and Biomedical Sciences.

In utero calves are especially vulnerable to infection. If they survive, they can remain infected for life, repeatedly spreading the virus to other cattle.

"They show up as normal cattle, but really, they're shedding a tremendous amount of virus. They're the 'Typhoid Marys' of BVDV spread," said Vander Ley, assistant director of UNL's Great Plains Veterinary Educational Center in Clay Center.

The cattle industry has vaccinated against the disease since the 1960s, but "the highly mutable nature of BVDV and the emergence of highly virulent strains of BVDV contribute to limited success of present control programs," the Academy of Veterinary Consultants has stated.

Scientists identified the specific genetic structure associated with the disease earlier this century. A collaborative project involving scientists with the USDA's Agricultural Research Service and Acceligen, a Minnesota-based private company, used gene editing to change the small number of amino acids that lead to BVDV vulnerability, while keeping the rest of the protein, CD46, unchanged.

"Our objective was to use gene-editing technology to slightly alter CD46 so it wouldn't bind the virus yet would retain all its normal bovine functions," said Aspen Workman, a scientist with the ARS U.S. Meat Animal Research Center (USMARC) in Clay Center, Nebraska.