The effect of bovine viral diarrhea virus (BVDV) strains on bovine monocyte-derived dendritic cells (Mo-DC) phenotype and capacity to produce BVDV

Abstract

BackgroundDendritic cells (DC) are important antigen presentation cells that monitor, process, and present antigen to T cells. Viruses that infect DC can have a devastating impact on the immune system. In this study, the ability of bovine viral diarrhea virus (BVDV) to replicate and produce infectious virus in monocyte-derived dendritic cells (Mo-DC) and monocytes was studied. The study also examined the effect of BVDV infection on Mo-DC expression of cell surface markers, including MHCI, MHCII, and CD86, which are critical for DC function in immune response.MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from bovine blood through gradient centrifugation. The adherent monocytes were isolated from PBMCs and differentiated into Mo-DC using bovine recombinant interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GMCSF). To determine the effect of BVDV on Mo-DC, four strains of BVDV were used including the severe acute non-cytopathic (ncp) BVDV2a-1373; moderate acute ncp BVDV2a 28508-5; and a homologous virus pair [i.e., cytopathic (cp) BVDV1b TGAC and ncp BVDV1b TGAN]. The Cooper strain of bovine herpesvirus 1 (BHV1) was used as the control virus. Mo-DC were infected with one of the BVDV strains or BHV-1 and were subsequently examined for virus replication, virus production, and the effect on MHCI, MHCII, and CD86 expression.ResultsThe ability of monocytes to produce infectious virus reduced as monocytes differentiated to Mo-DC, and was completely lost at 120 hours of maturation. Interestingly, viral RNA increased throughout the course of infection in Mo-DC, and the viral non-structural (NS5A) and envelope (E2) proteins were expressed. The ncp strains of BVDV down-regulated while cp strain up-regulated the expression of the MHCI, MHCII, and CD86 on Mo-DC.ConclusionsThe study revealed that the ability of Mo-DC to produce infectious virus was reduced with its differentiation from monocytes to Mo-DC. The inability to produce infectious virus may be due to a hindrance of virus packaging or release mechanisms. Additionally, the study demonstrated that ncp BVDV down-regulated and cp BVDV up-regulated the expression of Mo-DC cell surface markers MHCI, MHCII, and CD86, which are important in the mounting of immune responses.

Immune response to bovine viral diarrhea virus—looking at newly defined targets

“…B-cell levels in circulation are relatively normal (Gånheim et al, 2005) but B-cell depletion occurs extensively in the germinal centers of the lymph node (Liebler-Tenorio et al, 2002, 2003. Interestingly, there was no effect on circulating monocytes (Gånheim et al, 2005); although, in vitro infection of monocytes results in BVDV production (Brackenbury et al, 2003;Rajput et al, 2014). Likewise, during maturation from monocytes to monocyte-derived dendritic cells (MDDC), monocytes cultured in the presence of IL-4 and GM-SCSF initially produce virus, but within 48 h after in vitro culture, the virus yield is reduced and ceases altogether by 120 h in culture (Rajput et al, 2014).…”

“…Interestingly, there was no effect on circulating monocytes (Gånheim et al, 2005); although, in vitro infection of monocytes results in BVDV production (Brackenbury et al, 2003;Rajput et al, 2014). Likewise, during maturation from monocytes to monocyte-derived dendritic cells (MDDC), monocytes cultured in the presence of IL-4 and GM-SCSF initially produce virus, but within 48 h after in vitro culture, the virus yield is reduced and ceases altogether by 120 h in culture (Rajput et al, 2014). Interestingly, monocytederived macrophages (MDM) also fail to produce progeny virus Ley et al (2007).…”

“…Immune response to BVDV-looking at newly defined targets despite the presence of viral proteins and progeny viral RNA (Chase et al, 2004;Rajput et al, 2014). There is no effect on MDDC or MDM viability following BVDV infection (Chase et al, 2004;Rajput et al, 2014).…”

“…Immune response to BVDV-looking at newly defined targets despite the presence of viral proteins and progeny viral RNA (Chase et al, 2004;Rajput et al, 2014). There is no effect on MDDC or MDM viability following BVDV infection (Chase et al, 2004;Rajput et al, 2014). In BVDV-infected lymphoid tissue, macrophages and dendritic cells (DCs) appear to be uninfected although they are surrounded by apoptotic lymphocytes (Liebler-Tenorio et al, 2002, 2003.…”

BVDV Npro protein mediates the BVDV induced immunosuppression through interaction with cellular S100A9 protein

“…BVDV belongs to the Pestivirus genus of the Flaviviridae family. It an immunosuppressive virus and one of the major threats to the cattle industry worldwide [14][15][16][17][18]. BVDV has a positive sense single stranded RNA genome with the size of 12.3 Kb [19].…”