Detection and Diagnosis of BVDV in Cattle

At a Glance

Researchers have identified a white blood cell marker for (bovine) mothers that have been infected with non-cytopathic virus prior to development of the fetal immune system.
Why it Matters: The mothers seroconvert (develop antibodies and neutralize the virus), but the fetuses remain infected, and infect others after birth, which is the reason the virus persists.
The technology is specific to noncytopathic BVDV prior to the development of the fetal immune system but may have other applications to other non-bovine models of persistent viral infection.

Background

Bovine Viral Diarrhea Virus (BVDV) results in a loss of more than $400 million annually to beef and dairy producers. This is caused, to some degree, by current vaccines and vaccination programs that are not entirely efficacious. When infected during early pregnancy, immunocompetent pregnant cows clear the virus and become immune (seroconvert), but the fetus develops persistent viral infection. After birth, persistently infected calves that survive continually shed the virus and infect other cattle, thus allowing perpetuation of virus. Identification and elimination of persistently infected cattle are the most cost-effective measure to control and eradicate BVDV, thereby underscoring the critical need for an inexpensive and convenient diagnostic test.

Overview

Until recently, no known biomarkers were identified that distinguished between: vaccinated cattle that have seroconverted, infected mothers that seroconverted with acutely infected fetuses, infected mothers that seroconverted with persistently infected fetuses, and persistently infected cattle. This technology utilizes blood cell markers to identify and distinguish all of these conditions. Diagnostics based on the differential expression of these blood cell markers offer opportunities for more discerning identification of infected animals and would greatly benefit the successful implementation of control programs.

Figure 1. A graph showing select blood cell markers that are upregulated in bloods from persistently infected, when compared to non-infected steers using semi-quantitative Real Time PCR (GAPDH used as a control). The 28 kD (interferon induced 28 kD protein; CK771386), BST2 (bone marrow stromal cell surface antigen 2; CK846889), MX2 (myxovirus resistance 2; NM—173941) and ISG15 (Interferon stimulated 15 kDa; NM—174366) markers were all useful blood cell mRNA markers for distinguishing persistent viral infection (positive) when compared to control non-infected steers (negative). In this illustration, ISG15 and MX2 are preferred markers.

Benefits

Several platforms can utilize the biomarkers including microarray, qRT-PCR, and ELISA
Biomarkers distinguish between mothers carrying infected and uninfected fetuses
Biomarkers identify persistently infected cattle
Identified biomarkers may have additional application distinguishing between viral, bacterial, and other inflammatory infections

Publications

Virus Res. 2008 Mar;132 (1-2):49-58
Vet Pathol. 2008 May;45 (3):288-96
J Comp Pathol. 2008 Feb-Apr; 138(2-3):72-85. Epub 2008 Feb 25

Last Updated: October 2022

Opportunity

Collaboration and Funding Interest Welcome

IP Status

US Utility Patent: US 8435731 (Expired)

Inventors

Thomas R Hansen
Natalia P Smirnova
Kathleen J. Austin
Alberto L Van Olphen

Reference Number

08-031