Submitted to: Virus Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/22/2015
Publication Date: 6/1/2015
Publication URL: http://handle.nal.usda.gov/10113/61256
Citation: Schaut, R.G., McGill, J.L., Neill, J.D., Ridpath, J.F., Sacco, R.E. 2015. Bovine viral diarrhea virus type 2 in vivo infection modulates TLR4 responsiveness in differentiated Myeloid cells which is associated with decreased MyD88 expression. Virus Research. 208:44-55. DOI: 10.1016/j.viruses.2015.05.017.
Interpretive Summary: Bovine viral diarrhea virus (BVDV) can cause severe disease in cattle and possibly damage the immune system. This damage can lead to secondary infection. In this study, groups of calves were infected with BVDV. Some of the white blood cells were isolated during the course of infection and checked for their function. There was an observable decreased function in some of the white blood cells from the BVDV infected calves, which was also seen when the same cells were allowed to respond to bacterial components. These finding help to understand immune system function during infection and give insight into how the response to infection may be altered.
Technical Abstract: Bovine viral diarrhea virus (BVDV) causes clinical signs in cattle ranging from mild to severe acute infection which can lead to increased susceptibility to secondary bacteria. In this study we examined the effects of BVDV genotype 2 (BVDV2) infection on the ability of myeloid lineage cells derived from infected calves to produce proinflammatory cytokine mRNA and protein with or without bacterial LPS stimulation. Monocytes, monocyte-derived macrophages (MDMF), and alveolar macrophages (AMF), were chosen to represent differing stages of myeloid differentiation. It was found that monocytes isolated from infected calves produced higher levels of proinflammatory cytokine mRNA compared to uninfected calves and were hyperresponsive to LPS based on an increase in proinflammatory cytokine transcription and secretion. In contrast, MDMF inflammatory cytokine gene expression and secretion were, in general, significantly reduced compared to cells isolated from control calves. There was a discordance between AMF cytokine gene expression and protein secretion, in that while mRNA levels were significantly reduced, protein secretion was similar to that of stimulated cells from control animals. The differential cytokine expression of these macrophage cells was attributed to the modulated expression of myeloid differentiation primary response gene 88 (MyD88) protein and phosphorylated inhibitor of nuclear factor kappa-B kinase subunit beta (IKKß). Thus, BVDV2 infection results in the modulation of LPS-induced myeloid pro-inflammatory cytokine expression by effects on two separate components of TLR4 signaling cascades involving MyD88 and transcription factor NF'B activation.