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Surrogate markers for viral infections and other inflammatory responses

Inactive Publication Date: 2007-08-23
UNIVERSITY OF WYOMING
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0012] In accordance with the present invention, methods and compositions for diagnosis of Bovine Viral Diarrhea Virus (BVDV) are disclosed. Specifically, a simple, convenient test for accurately diagnosing BVDV is provided. The instant method provides the means to differentiate cattle persistently infected with BVDV (PI) from control non-infected steers. Other markers are provided which enable the skilled person to identify 1) heifers carrying persistently infected fetuses; 2) heifers carrying transiently virally infected fetuses and 3) heifers carrying control, uninfected fetuses. Such differentiation may be accomplished by detecting altered expression levels of one or more markers shown in Tables 1-9, or the proteins or peptide fragments encoded thereby. Most preferably, the test can be easily conducted in the field by veterinarians or cattle producers.

Problems solved by technology

Certain strains of BVDV can cause a hemorrhagic syndrome with high morbidity and moderate mortality in adult animals.
PI animals cannot eliminate the infecting BVDV from their system, and continuously release high amounts of virus in their bodily secretions and excretions, making them a continuous source of infection within the herd and potentially to other herds as well.
Furthermore, nursing PI calves can acutely infect their mothers and other normal nursing calves, which in turn infect their own mothers while they are pregnant, producing a new cycle of infection and eventually more PI calves.
Although these tests are widely used for the detection of PI animals they frequently fail to identify all infected animals (false negatives) resulting in the failure to remove all PI animals from the infected herd.
Moreover, serological tests cannot differentiate between PIs and uninfected animals, or between acutely infected and vaccinated animals.

Method used

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  • Surrogate markers for viral infections and other inflammatory responses
  • Surrogate markers for viral infections and other inflammatory responses
  • Surrogate markers for viral infections and other inflammatory responses

Examples

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example 1

[0115] Bovine viral diarrhea virus (BVDV) infections are responsible for important economic losses due to reproductive wastage, and respiratory and digestive disease in cattle. Infection of the early developing fetus frequently results in persistent infection (Pt). PI animals are the main source of new infection in herd mates. The complex host-viral interactions resulting from persistent infection are minimally understood, particularly in the bovine host. We hypothesized that gene expression would differ in bloods collected from PI when compared to non-infected steers. In preliminary studies, bloods were collected from three PI or three control steers and were processed to yield total cellular RNA. Labeled RNA was used to screen six independent bovine Affymetrix DNA chips, and analyzed for fold-changes at the University of Colorado Health Sciences Center Microarray Facility. The top 100 up-regulated genes belonged to MHC class I (45-fold), antiviral (32-100 fold), transcription fact...

example 2

[0127] We hypothesized that gene expression in white blood cells would differ in pregnant heifers carrying PI, TI or uninfected (control) fetuses. Non-vaccinated heifers were purchased, confirmed to be seronegative for BVDV and were placed on growing rations until they were old enough to be artificially inseminated and confirmed to be pregnant. Heifers were infected with noncytopathic BVDV2 on day 75 to generate PI fetuses, on day 175 to generate TI fetuses, or were not infected (n=6 heifers per treatment). Bloods were collected on days 0, 37, 75, 78, 82, 90, 120, 160, 175, 178, 182 and 190 of gestation for RNA, serology and virology. Fetuses were delivered on d. 190 by C-section and necropsied. Maternal blood mRNA on day 190 of gestation was screened using the bovine Affymetrix gene chips.

[0128] BVDV infection in heifers and fetuses was confirmed using ELISA and qRT-PCR. Infected pregnant heifers were seropositive for BVDV by days 15-45 post infection. PI fetuses weighed less and ...

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Abstract

Compositions and methods for the detection, diagnosis and treatment of BVDV and other viruses are provided.

Description

[0001] This application claims priority to U.S. provisional Application No. 60 / 757,965 filed Jan. 11, 2006, the entire contents of which are incorporated by reference herein.[0002] Pursuant to 35 U.S.C. Section 202(c), it is acknowledged that the United States Government has certain rights in the invention described herein, which was made in part with funds from the USDA / CSREES, grant numbers 2004-35204-14916 and 2004-35204-17005.FIELD OF THE INVENTION [0003] This invention relates to the field of molecular biology and virology. More specifically, the present invention provides materials and methods for the diagnosis and staging of bovine viral diarrhea virus (BVDV). BACKGROUND OF THE INVENTION [0004] Several publications and patent documents are cited throughout this application in order to more fully describe the state of the art to which this invention pertains. The disclosure of each of these citations is incorporated by reference herein. [0005] Bovine viral diarrhea virus (BVDV...

Claims

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Application Information

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IPC IPC(8): C12Q1/70C12Q1/68C12M3/00
CPCC12Q2600/158C12Q1/6883
Inventor HANSEN, THOMAS R.AUSTIN, KATHLEEN J.VAN OLPHEN, ALBERTOREMPEL, LEA A.
Owner UNIVERSITY OF WYOMING
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