ARS | Publication request: Bovine Viral Diarrhea Virus Modulation of Monocyte Derived Macrophage

Submitted to: American Association of Veterinary Laboratory Diagnosticians
Publication Type: Abstract Only
Publication Acceptance Date: July 28, 2010
Publication Date: November 11, 2010
Citation: Schaut, R.G., Ridpath, J.F., Neill, J.D., Sacco, R.E. 2010. Bovine Viral Diarrhea Virus Modulation of Monocyte Derived Macrophage [abstract]. American Association of Veterinary Laboratory Diagnosticians. p. 241.

Technical Abstract: Bovine Viral Diarrhea Virus (BVDV) is a single stranded, positive sense virus of the Flaviviridae family and is the causative agent of the disease known as Bovine Viral Diarrhea (BVD). Disease can range from persistently infected (PI) animals displaying no clinical symptoms of disease to an acute, severe sickness, with bloody diarrhea, high fever, mouth ulcers, and pneumonia. PI animals are the result of infection with a noncytopathic (NCP) BVDV in utero, which results in immune tolerance, and lifelong infection. Superinfection of PI animals with cytopathic (CP) virus, may lead to a fatal syndrome called mucosal disease. The role of BVDV as primarily a respiratory pathogen remains controversial. Experimental studies have indicated mild clinical respiratory disease and interstitial pneumonia induced in 4- to 6-month-old calves inoculated with BVDV. However, most studies have focused on BVDV1 role in immunosuppression. Limited studies to date have focused on the macrophage cytokine response to BVDV2. Therefore, we have compared macrophage cytokine responses to four strains of BVDV2 of differing biotype and virulence. Monocyte derived macrophages (MDM) displayed an altered cytokine response after inoculation with the four strains of BVDV2. With the cytopathic and high virulence BVDV2 strains, we observed a greater initial induction (2 hours post inoculation) of pro-inflammatory cytokines such as IL-1beta, IL-12p40, and TNF-alpha. However, this response is not sustained, and a significant decrease in transcription between 4-6 hours post inoculation was observed. Furthermore, results of others have indicated that gene transcription of Major Histocompability Complex (MHC) II and CD80/86 of monocytes inoculated with BVDV1 were down regulated by 24 hours post inoculation. MDMs are professional antigen presenting cells (APC) with the ability to activate an adaptive response via MHC class II expression and proper co-stimulation to T cells. Our results and those of others, suggest that BVDV may alter the ability of antigen presenting cells to prime a productive T cell response respond by modulating cytokine, MHC class II and CD80/86 expression. Loss of function in APCs is one means by which BVDV could modulate the immune response to other pathogens. These studies indicate that infection of MDM with BVDV can be used as an in vitro model to study alterations in immunoregulatory pathways that leads to immunosuppression.