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Bovine neonatal pancytopenia (BNP), often referred to as bleeding calf syndrome, is a disease in calves caused by the destruction of the calf’s bone marrow. Though the relative number of affected calves in each herd is low, usually less than 1 percent, BNP is highly lethal and the majority of affected calves die. Recent evidence on the disease’s etiology points towards an association between PregSure®, a specific vaccine against Bovine Virus Diarrhoea Virus (BVDV), and BNP pathogenesis in calves, but the immunological response underlying this remains unclear.

Christa Kühn and colleagues based at the Leibniz Institute for Farm Animal Biology and the Freie Universität Berlin, Germany, present a new analysis in Veterinary Research, using novel deep sequencing techniques to monitor immune response to the vaccination that has been associated with BNP.

In the study, 12 cows aged three to five years received a basic double vaccination with inactivated BVDV vaccine, and four of these cows had calves that developed BNP. The authors sequenced the RNA of blood samples collected from the cows immediately prior to vaccination and 14 days after.

Deep sequencing of the blood transcriptome indicated what the authors described as “a massive contamination of the vaccine”. BVDV is a single-stranded RNA virus, so it’s especially striking that post-vaccination RNA sequencing revealed a coordinated and specific immune response to double-stranded RNA (or possibly a dsRNA analogue). As well as significant T cell activation, the immune response to dsRNA included significant upregulation of genes in the EIF2, RIG I and TLR3 signalling pathways.

By using deep RNA sequencing to evaluate gene expression, in response to vaccination with the inactivated BVDV vaccine, the authors also discovered what appears to be a new cytokine-like gene in the bovine genome: XLOC_032517.

There is no annotation of the locus XLOC_032517 in any other species, though it had the most significant difference in expression related to vaccination, among all loci identified the study. It’s possible that the gene is directly linked to ruminant immune response.

Further immunological analysis will reveal more about the links between BVDV vaccination, immune response in cattle, and the onset of bleeding calf syndrome. Kühn and colleagues have presented the first ever application of next generation deep RNA sequencing to monitor the response to a viral vaccine in a livestock or companion animal species, discovering a new cytokine-like locus in the process.


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