The whole genome sequencing offers insights into the susceptibility to the foot-and-mouth disease virus carrier state.

Foot-and-mouth disease virus (FMDV) establishes persistent infection in more than 50% of infected ruminants, irrespective of vaccination status, implicating potential contributions of host genetic variations to viral persistence. In this study, we conducted whole-genome resequencing of a cohort of 22 cattle, comprising 7 carriers and 15 noncarriers. Clean reads were mapped to the cattle (Bos taurus) reference genome (ARS-USD1.2) and cattle-yak (Bos taurus × Bos grunniens) haplotype assemblies. We identified 24 shared carrier-specific variants across genomes and 31 carrier-specific variants restricted to the cattle-yak haplotypes. These carrier‑specific variants were primarily located in genes involved in olfactory perception, cell development and morphological maintenance, transcriptional and translational regulation, signal transduction, metabolic homeostasis, stress resistance, and immune cell regulation. The combined functional impact of these variants may influence innate immune regulatory capacity and shape the magnitude of adaptive immune activation, thereby conferring distinct antiviral capacities and facilitating viral persistence. Our findings offer a comprehensive catalog of candidate genetic variants potentially associated with persistent FMDV infection, providing novel insights into the genetic architecture underlying host's susceptibility to viral persistence.