Differential effects of bovine viral diarrhoea virus on monocytes and dendritic cells

Abstract

Various pathogens have been shown to infect antigen-presenting cells and affect their capacity to interact with and stimulate T-cell responses. We have used an antigenically identical pair of noncytopathic (ncp) and cytopathic (cp) bovine viral diarrhoea virus (BVDV) isolates to determine how the two biotypes affect monocyte and dendritic cell (DC) function. We have shown that monocytes and DCs are both susceptible to infection with ncp BVDV and cp BVDV in vitro. In addition, monocytes infected with ncp BVDV were compromised in their ability to stimulate allogeneic and memory CD4+ T cell responses, but DCs were not affected. This was not due to down-regulation of a number of recognized co-stimulatory molecules including CD80, CD86 and CD40. Striking differences in the response of the two cell types to infection with cytopathic virus were seen. Dendritic cells were not susceptible to the cytopathic effect caused by cp BVDV, whereas monocytes were killed. Analysis of interferon (IFN)-a/b production showed similar levels in monocytes and DCs exposed to cp BVDV, but none was detected in cells exposed to ncp BVDV. We conclude that the prevention of cell death in DCs is not associated with enhanced production of IFN-a/b, as proposed for influenza virus, but is by a distinct mechanism.

Peripheral blood mononuclear cells from field cattle immune to bovine viral diarrhea virus (BVDV) are permissive in vitro to BVDV

“…Hence, humoral response against BVDV alone may not be adequate for efficient clearance of BVDV from PBMCs of BVDV infected animals. It has been shown previously that infection of antigen presenting cells in PBMCs with BVDV can adversely affect their ability to interact with and stimulate T-cell responses which may be a critical viral strategy for immune evasion (Glew et al, 2003). Our results revealed that in PBMCs from BVDV-1 and BVDV-2-immune cattle, the viral load of heterologous virus was more than the homologous virus indicating that cell-mediated immune response is involved in determination of viral load.…”

“…These cells include granulocytes, monocytes, null cells, macrophages, antigen-presenting cells, myeloid cells, CD4+ and CD8+ T-lymphocytes and B cells (Chase et al, 2004). Of these, the B cells population seems to make only minor contribution (Ohmann et al,1987), while infection of antigen presenting cells with BVDV perturbs the normal pathway of immune stimulation thereby leading to immune evasion and chronic infection (Glew et al, 2003).…”

Understanding the Pathogenesis of Cytopathic and Noncytopathic Bovine Viral Diarrhea Virus Infection Using Proteomics

“…In addition, cp BVDV readily trigger IFN type-I whereas infection with ncp BVDV fails to induce IFN generation (Peterhans et al 2003). Also, BVDV has been reported to modulate functions of immune cells after infection in vitro including increased production of nitric oxide from infected macrophages (Adler et al 1994), decreased production of TNF-from activated macrophages (Adler et al 1994), inhibited phagocytosis of alveolar macrophages (Brewoo et al 2007) and decreased Tstimulatory ability of monocytes (Glew et al 2003). Phagocytosis and macropinocytosis antigen uptake mechanisms play a crucial role in the innate immune responses by clearing pathogens at sites of infection.…”

Bovine Viral Diarrhea Virus Infections

“…19,79,89,117,119 BVDV infects a wide variety of cell types but has a predilection for cells of the immune system such as monocytes/macrophages, dendritic cells (DCs), and lymphocytes. 19,61,90 The consequences of infection include the death of these cell populations as an extreme event or more subtle effects on cytokine expression and synthesis of costimulatory molecules. 18,26,61,119 The changes in cytokine production by immune or nonimmune cells affect both innate and adaptive immunity.…”

“…19,61,90 The consequences of infection include the death of these cell populations as an extreme event or more subtle effects on cytokine expression and synthesis of costimulatory molecules. 18,26,61,119 The changes in cytokine production by immune or nonimmune cells affect both innate and adaptive immunity. 108 The persistently infected (PI) animal serves as the reservoir of BVDV and a source of infection.…”