A collaboration between scientists from government, academia and industry sectors has successfully produced the first gene-edited calf with resistance to bovine viral diarrhea virus (BVDV), a disease that costs the U.S. cattle industry billions of dollars annually. A study recently published in Proceedings of the National Academy of Sciences (PNAS) Nexus details the partnership between researchers from USDA’s Agricultural Research Service (ARS), the University of Nebraska – Lincoln, the University of Kentucky, Acceligen and Recombinetics Inc.
Since it was first recognized in the 1940s, BVDV has remained one of the most impactful viruses in cattle worldwide. Though the virus does not affect humans, it is highly contagious among cattle and can cause severe respiratory and intestinal illness. The disease can prove especially harmful to pregnant cows because of its ability to infect calves in utero, causing spontaneous abortions and low birth rates. Some infected calves survive to birth and remain infected for life, shedding huge amounts of the virus to other cattle. And although BVDV vaccines have been available for more than 50 years, they are not always effective in stopping the transmission of the disease.
However, over the past 20 years, researchers have discovered the main cellular receptor (CD46) and the area where the virus binds to that receptor and causes infection in cows. Scientists modified the virus binding site in this recent study to block infection.
Ginger, seen here at 18 months, offers hope for a future with significantly less cattle industry pressure from BVDV and less dependence on antibiotics. Photo courtesy of USDA-ARS.
“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,” says Aspen Workman, lead author and researcher at the ARS U.S. Meat Animal Research Center in Clay Center, Nebraska.
After seeing promising outcomes in the laboratory, Acceligen edited cattle skin cells to develop embryos carrying the altered gene. These embryos were transplanted into surrogate cows to test whether this approach might also reduce virus infection in live animals.
The method worked, and the first CD46 gene-edited animal, a Gyr heifer named Ginger, was born healthy on July 19, 2021. The calf was observed for several months before being introduced to the virus to determine whether she could become infected. She was housed for a week with a BVDV-infected dairy calf that was born shedding the virus. Ginger’s cells displayed significantly reduced susceptibility to the virus, and she showed no observable adverse health effects. She will continue to be closely observed to monitor her own health and ability to produce and raise healthy calves.
The researchers and ARS believe this proof-of-concept study demonstrates the possibility of reducing the burden of BVDV-associated diseases in cattle through gene editing. And because BVDV infection also puts calves at risk for secondary bacterial diseases, Ginger also represents another potential opportunity to decrease the industry’s need for antibiotics. While promising, this trait is still in the research phase, and no associated beef is yet scheduled to enter the U.S. food supply.
