Abstract
INTRODUCTION: The Bovine Viral Diarrhea Virus 1 (BVDV1) and HoBi-like virus (BVDV3), both within the same genus, share genomic homology and exhibit low antigenic cross-reactivity despite presenting similar clinical manifestations. In 2021, a bovine respiratory disease complex (BRDC) outbreak on two cattle farms in the Inner Mongolia Autonomous Region of China resulted in ten fatalities. METHODS: Metagenomic and metatranscriptomic analyses were used to identify viral agents, including a co-infection case. A genetic evolution analysis assessed the relationships with related strains. Experimental infections in guinea pigs and calves evaluated the pathogenicity of the viruses. RESULTS: Phylogenetic analysis of the BVDV3 isolate IM2201 revealed close relatedness to Brazilian strains, with 97.06% nucleotide homology to the highly virulent strain SV478/07. Experimental co-infection in guinea pigs resulted in more severe clinical signs, including fever, cough, diarrhea, and significant pathological changes, and led to a higher mortality rate (40%) compared to no mortality from single-virus infections with BVDV1 or BVDV3. Similarly, co-infected cattle exhibited more severe clinical signs, including bloody diarrhea and rectal temperatures exceeding 40°C, along with persistent viremia and nasal viral shedding from 7 to 21 days post-infection. Blood analysis revealed significant reductions in white blood cell counts, particularly in co-infected cattle. DISCUSSION: This study highlights the enhanced pathogenicity and synergistic effects of BVDV1 and BVDV3 co-infection, exacerbating disease severity.