Abstract

As one of the major pathogens, bovine viral diarrhea virus caused a significant economic loss to the livestock industry worldwide. Although BVDV infections have increasingly been reported in China in recent years, the molecular aspects of those BVDV strains were barely characterized. In this study, we reported the identification and characterization of a novel BVDV isolate designated as SD-15 from cattle, which is associated with an outbreak characterized by severe hemorrhagic and mucous diarrhea with high morbidity and mortality in Shandong, China. SD-15 was revealed to be a noncytopathic BVDV, and has a complete genomic sequence of 12,285 nucleotides that contains a large open reading frame encoding 3900 amino acids. Alignment analysis showed that SD-15 has 93.8% nucleotide sequence identity with BVDV ZM-95 isolate, a previous BVDV strain isolated from pigs manifesting clinical signs and lesions resembling to classical swine fever. Phylogenetic analysis clustered SD-15 to a BVDV-1m subgenotype. Analysis of the deduced amino acid sequence of glycoproteins revealed that E2 has several highly conserved and variable regions within BVDV-1 genotypes. An additional N-glycosylation site (240NTT) was revealed exclusively in SD-15-encoded E2 in addition to four potential glycosylation sites (Asn-X-Ser/Thr) shared by all BVDV-1 genotypes. Furthermore, unique amino acid and linear epitope mutations were revealed in SD-15-encoded Erns glycoprotein compared with known BVDV-1 genotype. In conclusion, we have isolated a noncytopathic BVDV-1m strain that is associated with a disease characterized by high morbidity and mortality, revealed the complete genome sequence of the first BVDV-1m virus originated from cattle, and found a unique glycosylation site in E2 and a linear epitope mutation in Erns encoded by SD-15 strain. Those results will broaden the current understanding of BVDV infection and lay a basis for future investigation on SD-15-related pathogenesis.

Highlights

  • Bovine viral diarrhea virus (BVDV) is a small, enveloped virus with a single-stranded, positivesense RNA genome

  • We have isolated a noncytopathic BVDV-1m strain that is associated with a disease characterized by high morbidity and mortality, revealed the complete genome sequence of the first BVDV-1m virus originated from cattle, and found a unique glycosylation site in E2 and a linear epitope mutation in Erns encoded by SD-15 strain

  • SD-15 is a noncytopathic BVDV strain isolated in this study from cattle newly introduced to Shandong from Zemeng County of the Inner Mongolia autonomous regions

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Summary

Introduction

Bovine viral diarrhea virus (BVDV) is a small, enveloped virus with a single-stranded, positivesense RNA genome. Together with classical swine fever virus (CSFV) and border disease virus (BDV), BVDV belongs to the genus of pestivirus within the family of Flaviviridae [1]. As one of the most important viral pathogens, BVDV causes significant economic losses to cattle industry worldwide [2,3,4]. While the epidemic isolates for BVDV mainly belong to BVDV-1, the more recent hypervirulent BVDV-2 strains have been isolated from cattle with acute diarrhea and fatal thrombocytopenia [11,12,13]. Genomic sequence comparisons revealed the diversity and genetic variability of BVDV strains isolated from different herds or even in the same herd [13]. Based on the genetic variability, seventeen BVDV-1 subgenotypes and four BVDV-2 subgenotypes have been reported so far [14,15,16,17,18]

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