Bovine viral diarrhea virus type 2 in vivo infection modulates TLR4 responsiveness in differentiated myeloid cells which is associated with decreased MyD88 expression

Abstract

Symptoms of bovine viral diarrhea virus (BVDV) infection range from subclinical to severe, depending on strain virulence. Several in vitro studies showed BVDV infection impaired leukocyte function. Fewer studies have examined the effects of in vivo BVDV infection on monocyte/macrophage function, especially with strains of differing virulence. We characterized cytokine production by bovine myeloid cells isolated early or late in high (HV) or low virulence (LV) BVDV2 infection. Given BVDV infection may enhance susceptibility to secondary bacterial infection, LPS responses were examined as well. Monocytes from HV and LV infected calves produced higher levels of cytokines compared to cells from controls. In contrast, monocyte-derived macrophage cytokine levels were generally reduced. Modulated cytokine expression in HV BVDV2 macrophages was associated with decreased MyD88 expression, likely due to its interaction with viral NS5A. These data and those of others, suggest that certain Flaviviridae may have evolved strategies for subverting receptor signaling pathways involving MyD88.

Bovine Viral Diarrhea Virus Type 2 Impairs Macrophage Responsiveness to Toll-Like Receptor Ligation with the Exception of Toll-Like Receptor 7

“…Peripheral blood mononuclear cells were isolated and red blood cells (RBC) lysed with buffered ammonium chloride salt solution [ 21 ]. After RBC lysis, cells were washed with sterile phosphate-buffered saline (PBS).…”

“…Cells were resuspended in complete RPMI 1640 (cRPMI) containing 10% fetal bovine serum (tested commercially and in house to be free of BVDV and antibodies against BVDV), 2 mM L-glutamine, 1% antibiotic–antimycotic solution, and gentamicin sulfate (Life Technologies—Gibco, Carlsbad, CA). Monocytes were isolated by plastic adherence for 2 h as previously described [ 21 ]. Ice-cold PBS was added to the plate and adherent cells were removed with a cell scraper.…”

“…These pro-inflamatory cytokines have been shown to have an anti-viral role [ 16 , 18 – 20 ] and subsequently the secretion and pathways involved in induction of these cytokines are targets of pathogens. We found that differentiated MΦ isolated after an in vivo BVDV2 infection are impaired in their response to TLR4 ligation [ 21 ]; however ligation of other TLRs have yet to be fully explored.…”

Çin’de BVDV 1q’nun Tespiti: Patojenitesinin Araştırılması Amacıyla Genetik Karakterizasyon ve Deneysel Enfeksiyon

“…Histopathological observations showed lymphoid depletion and shedding of the villi of the small intestine. Many studies have reported that animals infected with non BVDV show leukocyte depletion, failure to induce the production of type I interferon α/β, immune suppression, and often secondary infections [32][33][34][35] .…”

The Immunology of Bovine Respiratory Disease

“…33 Similarly, in vivo BVDV infection also modulates the capacity of monocytes and macrophages to respond via TLR4. 34 Like BVDV, several other viruses have an impact on APC activation and function. PIV infection suppresses macrophage phagocytosis and inhibits oxidative burst.…”