Bovine viral diarrhoea virus 1b infection associated with congenital tremor and hypomyelination in Holstein calves

• Published in: Veterinary microbiology Vol. 256; p. 109047
• Main Authors: Gallina, Laura, Koch, Michel C., Gentile, Arcangelo, Treglia, Ida, Bombardi, Cristiano, Mandrioli, Luciana, Bolcato, Marilena, Scagliarini, Alessandra, Drögemüller, Cord, Seuberlich, Torsten, Ciulli, Sara
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2021; Elsevier BV
• Subjects: Ataxia; Blood; Bovine viral diarrhoea virus; Cerebellum; Coding; Congenital infection; Congenital tremor; Diarrhea; Genetic variability; Genomes; Genotypes; Hypomyelination; Hypoplasia; Infections; Neurological diseases; Pestivirus; Phenotypes; Structural proteins; Tremor; Viruses; Whole genome sequencing; Pestivirus; Congenital tremor; Bovine viral diarrhoea virus; Hypomyelination; Whole-genome sequencing
• ISSN: 0378-1135; 1873-2542
• DOI: 10.1016/j.vetmic.2021.109047

•Hypomyelination is a rare consequence of in utero BVDV infection in cattle.•A high prevalence congenital tremor and hypomyelination BVD outbreak is described.•The complete genome of a BVDV causing hypomyelination is reported for the first time.•Type and number of viral genomic mutations differ between brain and blood samples.•Genetic variability and host factors contributed to the unusual BVD outbreak. Hypomyelination is a rare consequence of in utero bovine viral diarrhoea virus (BVDV) infection. We describe a BVDV outbreak in a naïve Holstein dairy herd in northern Italy, with an unusually high prevalence of calves with neurological signs, generalised tremors and ataxia. Histological analysis showed that hypomyelination was the predominant lesion and that the most typical BVDV neuropathological findings (e.g. cerebellar hypoplasia) were absent. Virological and molecular analyses showed that non-cytopathic BVDV genotype 1b was associated with the calves’ neurological signs and excluded other viruses responsible for congenital infection or neurological disorders. Whole-genome sequencing of BVDVs from the brain of a calf with neurological signs and the whole blood of a persistently infected herd-mate with no such sign showed >99.7 % sequence identity. Analysis of the quasispecies distribution revealed the greatest variation rates in regions coding for the structural proteins E1 and E2. Variation was slightly greater in the brain- than in the blood-derived sequence and occurred at different sites, suggesting the occurrence of distinct evolutionary processes in the two persistently infected calves. Molecular characterisation of BVDV genomes from five other calves with neurological signs from the same farm confirmed that the E1 and E2 regions were the most variable. Several factors, including genetic variability and host factors, appear to have contributed to the observed unique BVDV disease phenotype, characterised by hypomyelination and neurological signs.