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Gene-Editing Creates First BVDV-Resistant Calf

Scientists have partnered to create the first gene-edited calf with resistance to bovine viral diarrhoea virus, a virus that costs the cow industry in the United States billions of dollars each year. The USDA’s Agricultural Research Service, the University of Nebraska-Lincoln, the University of Kentucky, and industry partners Acceligen and Recombinetics, Inc. collaborated on the latest research.

The bovine viral diarrhoea virus is one of the most serious viruses impacting the health and well-being of cattle globally, and experts have been researching it since it was discovered in the 1940s. Although this virus has no effect on humans, it is very infectious among cattle and may cause serious respiratory and intestinal problems.

BVDV may be fatal to pregnant cows because it infects developing calves, resulting in spontaneous abortions and poor birth rates. Some infected calves live to birth and are permanently infected, releasing huge quantities of virus to other cattle. Despite the availability of vaccinations for more than 50 years, managing BVDV illness remains a challenge since immunisations are not always successful in halting transmission.
However, scientists have uncovered the major cellular receptor (CD46) and the location where the virus attaches to that receptor, producing infection in cows during the last 20 years. In this latest work, scientists changed the viral binding site to prevent infection.
“Our goal was to use gene-editing technology to slightly alter CD46 so it wouldn’t bind the virus but would retain all of its normal bovine functions,” said Aspen Workman, lead author and researcher at ARS’ U.S. Meat Animal Research Centre (USMARC) in Clay Centre, Nebraska.
This hypothesis was initially explored in cell culture by the researchers. Acceligen manipulated bovine skin cells to create embryos with the changed gene after witnessing encouraging results in the lab. These embryos were implanted into surrogate cows to see whether this method may help minimise viral infection in living animals.
It worked, and Ginger, the first CD46 gene-edited calf, was born healthily on July 19, 2021. The calf was monitored for many months before being challenged with the virus to see whether she may get sick. She was kept with a BVDV-infected dairy calf that was born shedding virus for a week. Ginger’s cells were substantially less susceptible to BVDV, resulting in no obvious detrimental health consequences.
Ginger’s health and capacity to conceive and nurture her own calves will be continuously monitored by the experts.
This proof-of-concept research shows that gene editing has the potential to reduce the burden of BVDV-associated illnesses in cattle. Because BVDV infection puts calves at risk for secondary bacterial infections, the altered calf provides another possible possibility to reduce the requirement for antibiotics in agriculture. This intriguing characteristic is still in the research stage, and no linked beef is currently entering the US food supply.
The Agricultural Research Service is the primary scientific in-house research organisation of the United States Department of Agriculture. ARS works every day to find answers to agricultural challenges that impact America. Each dollar spent in agricultural research in the United States has a $20 economic effect.

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