Scientists have collaborated to produce the first gene-edited calf resistant to bovine viral diarrhea virus (BVDV). This achievement has excellent potential to alleviate the billions of dollars this disease costs the domestic cattle sector annually.
The recent study published in PNAS Nexus results from a collaboration between the USDA’s Agricultural Research Service (ARS), the University of Nebraska–Lincoln (UNL), the University of Kentucky, and industry partners, Acceligen and Recombinetics, Inc.
Why the Science Matters
BVDV is one of the most significant viruses affecting the health and well-being of cattle worldwide. While not infecting humans directly, this virus is highly contagious among cattle and can cause severe respiratory and intestinal diseases.
BVDV can be disastrous to pregnant cows because it can infect developing calves, causing spontaneous abortions and low birth rates. Some infected calves survive to birth and remain infected for life, shedding massive amounts of virus to other cattle. Controlling BVDV disease remains a problem as vaccines currently available are not always effective in stopping transmission.
In 1986, the scientific community discovered the primary cellular receptor (CD46) and the area where the virus binds to that receptor, causing infection in cows. Scientists in this breakthrough calf model, modified the virus binding site in this recent study to block infection.
Researchers at ARS’ U.S. Meat Animal Research Center (USMARC) in Clay Center, Nebraska, said, “Our objective was to use gene-editing technology to alter CD46 slightly so it wouldn’t bind the virus yet would retain all its normal bovine functions.”
https://www.ars.usda.gov/plains-area/clay-center-ne/marc/
The scientists first tested this idea in cell culture, and after seeing positive 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 reduce virus infection in live animals.
The first CD46 gene-edited calf, named Ginger, was born healthy on July 19, 2021. The calf was observed for several months and then later challenged with the virus to determine if she could become infected. To ensure exposure, she was housed for a week with a BVDV-infected dairy calf born actively shedding the virus. Ginger’s cells displayed significantly reduced susceptibility to BVDV, which resulted in no observable adverse health effects.
The scientists will continue to closely observe Ginger’s health and ability to produce and raise her calves.
This proof-of-concept study demonstrates the possibility of gene editing reducing the burden of BVDV-associated diseases in cattle. The edited calf also represents another potential opportunity to lessen the need for antibiotics in agriculture since BVDV infection also puts calves at risk for secondary bacterial diseases. This promising trait is still in the research phase, and no associated beef is currently entering the U.S. food supply.