Primary Cells from a <i>CD46</i>-Edited Bovine Heifer Have Reduced BVDV Susceptibility Despite Viral Adaptation to Heparan Sulfate.

ABSTRACT: A precision genome edit in the bovine CD46 gene (A₈₂LPTFS₈₇) dramatically reduced bovine viral diarrhea virus (BVDV) susceptibility in a cloned heifer. However, pathogen evolution threatens the long-term efficacy of such interventions. Here, our aim is two-fold: first, to determine whether BVDV can adapt in vitro to use the edited CD46 receptor to infect Madin-Darby bovine kidney (MDBK) cells, and second, to evaluate the ex vivo infectivity of culture-adapted viruses in cells from the CD46-edited heifer. Serial passage of BVDV on CD46-edited MDBK cells selected for virus variants capable of CD46-independent infection. Virus genome sequencing revealed mutations in the viral E^RNS gene predicted to enhance HS-mediated entry. HS adaptation

SUBMITTER: Krueger AC 

PROVIDER: S-EPMC12116123 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature