scholarly journals Bungowannah Pestivirus Chimeras as Novel Double Marker Vaccine Strategy against Bovine Viral Diarrhea Virus

Vaccines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 88
Author(s):  
Susanne Koethe ◽  
Patricia König ◽  
Kerstin Wernike ◽  
Jana Schulz ◽  
Ilona Reimann ◽  
...  

Marker or DIVA (differentiation of infected from vaccinated animals) vaccines are beneficial tools for the eradication of animal diseases in regions with a high prevalence of the designated disease. Bovine viral diarrhea virus (BVDV)-1 (syn. Pestivirus A) is a flavivirus that infects predominantly cattle resulting in major economic losses. An increasing number of countries have implemented BVDV eradication programs that focus on the detection and removal of persistently infected cattle. No efficient marker or DIVA vaccine is yet commercially available to drive the eradication success, to prevent fetal infection and to allow serological monitoring of the BVDV status in vaccinated farms. Bungowannah virus (BuPV, species Pestivirus F), a related member of the genus Pestivirus with a restricted prevalence to a single pig farm complex in Australia, was chosen as the genetic backbone for a marker vaccine candidate. The glycoproteins E1 and E2 of BuPV were substituted by the heterologous E1 and E2, which are major immunogens, of the BVDV-1 strain CP7. In addition, the candidate vaccine was further attenuated by the introduction of a deletion within the Npro protein coding sequence, a major type I interferon inhibitor. Immunization of cattle with the chimeric vaccine virus BuPV_ΔNpro_E1E2 CP7 (modified live or inactivated) followed by a subsequent experimental challenge infection confirmed the safety of the prototype strain and provided a high level of clinical protection against BVDV-1. The serological discrimination of vaccinated cattle could be enabled by the combined detection of BVDV-1 E2- in the absence of both BVDV NS3- and BVDV Erns-specific antibodies. The study demonstrates for the first time the generation and application of an efficient BVDV-1 modified double marker vaccine candidate that is based on the genetic background of BuPV accompanied by commercially available serological marker ELISA systems.

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Yu Deng ◽  
Silu Wang ◽  
Runxia Liu ◽  
Guiying Hao

Bovine viral diarrhea virus (BVDV) affects cows, pigs, sheep, goats, and other ruminants, as well as some wild animals. BVDV causes considerable economic losses every year and many countries have developed programs aimed at the eradication of this disease. The genetic diversity of BVDV in diseased goats has never been described in southwestern China. Thus, in this study, we applied antigen-capture ELISA and RT-PCR to survey the infection rate of BVDV in diseased goats in this region. Our results demonstrated that the average BVDV infection rate in goats was 17.51%, with all positive samples indicating infection by BVDV-1 and not BVDV-2, BVDV-3, or Border disease virus. The molecular characteristics of the 5′-untranslated region (5′-UTR) of BVDV-1 were recognized as belonging predominantly to the BVDV-1a, 1b, 1c, 1m, and 1p subtypes. BVDV-1b and 1m were the most abundant subtypes identified in this region, similar to the BVDV epidemics in cattle in other regions of China. This is the first study that describes the genetic characterization of BVDV in sick goats from southwestern China and is important for future studies and control programs.


2020 ◽  
Vol 103 (3) ◽  
pp. 560-571 ◽  
Author(s):  
Hanah M Georges ◽  
Katie J Knapek ◽  
Helle Bielefeldt-Ohmann ◽  
Hana Van Campen ◽  
Thomas R Hansen

Abstract Bovine viral diarrhea virus continues to cost the cattle industry millions of dollars each year despite control measures. The primary reservoirs for bovine viral diarrhea virus are persistently infected animals, which are infected in utero and shed the virus throughout their lifetime. The difficulty in controlling the virus stems from a limited understanding of transplacental transmission and fetal development of immunotolerance. In this study, pregnant bovine viral diarrhea virus naïve heifers were inoculated with bovine viral diarrhea virus on day 75 of gestation and fetal spleens were collected on gestational days 82, 97, 190, and 245. Microarray analysis on splenic RNA from days 82 and 97 revealed an increase in signaling for the innate immune system and antigen presentation to T cells in day 97 persistently infected fetuses compared to controls. Reverse transcription quantitative polymerase chain reaction on select targets validated the microarray revealing a downregulation of type I interferons and lymphocyte markers in day 190 persistently infected fetuses compared to controls. Protein was visualized using western blot and tissue sections were analyzed with hematoxylin and eosin staining and immunohistochemistry. Data collected indicate that fetal immunotolerance to bovine viral diarrhea virus developed between days 97 and 190, with mass attenuation of the immune system on day 190 of gestation. Furthermore, lymphocyte transcripts were initially unchanged then downregulated, suggesting that immunotolerance to the virus stems from a blockage in lymphocyte activation and hence an inability to clear the virus. The identification of lymphocyte derived immunotolerance will aid in the development of preventative and viral control measures to implement before or during pregnancy.


2008 ◽  
Vol 20 (1) ◽  
pp. 156 ◽  
Author(s):  
A. Bielanski ◽  
J. Algire ◽  
A. Lalonde

Bovine viral diarrhea virus (BVDV) infection affects cattle throughout the world. It causes significant economic losses in the cattle industry. The potential for transmission of a cytopathic biotype of BVDV by in vivo-derived embryos has been thought to be negligible. However, there is no study to prove non-transmission of the most common field isolate of noncytopathic biotype (NCPB) of BVDV by IVF embryos. Here we report on the preliminary outcome of embryo transfer (ET) of IVF embryos exposed in vitro to type-1 (NY-1) and type-2 (P-131) genotypes of NCPB of BVDV. For this experiment, IVF embryos were generated using standard methods which briefly involve: maturation of cumulus–oocyte complexes in TCM medium, fertilization of oocytes with BVDV-free semen, and culture of zygotes to the blastocyst stage in SOF medium without somatic cells. Day 7 blastocysts were exposed for 1 h to NY-1 or P-131 (103–107 TCID50 mL–1) BVDV strains before being washed (without trypsin) as recommended by IETS. Two embryos were transferred on each occasion. Embryo recipients were virus-free and anti-BVDV antibody-free prior to ET. The recipients remained individually in isolation premises after ET. In total, 126 ET procedures were performed resulting in 57 pregnancies and 34 calves born free of the infectious virus and BVDV antibodies (5 pregnancies are still pending). In total, 23 pregnancies were lost after 30 days. Exposure of embryos to type-2 BVDV resulted in a loss of 46% (17/37) of pregnancies after 30 days post-ET and 20 recipients seroconverted to BVDV. Within seroconverted and pregnant animals (n = 14), only 2 recipients maintained pregnancy and delivered uninfected calves at term. In contrast, exposure of embryos to type-1 caused 30% (6/20) of the pregnancy losses after 30 days and did not cause any seroconversion in ET recipients. After washing, 33% (3/9) and 38% (17/44) single embryos from the infected pool of IVF embryos tested positive for the BVDV. In conclusion, under these experimental conditions, a proportion of recipients was apparently infected after receipt of BVDV-exposed embryos. However, all of the calves that survived to term were BVDV-free and anti-BVDV antibody free.


2005 ◽  
Vol 17 (5) ◽  
pp. 461-463 ◽  
Author(s):  
Margaret A. Miller ◽  
José A. Ramos-Vara ◽  
Steven B. Kleiboeker ◽  
Robert L. Larson

The effects of delayed or prolonged fixation on immunohistochemical detection of bovine viral diarrhea virus (BVDV) antigen were evaluated in skin. Ear-notch specimens from 2 calves persistently infected with BVDV type 1 were handled in 1 of 3 ways: 1) fixed in formalin promptly and processed for immunohistochemistry (IHC) after 3–176 days; 2) held at 3–4°C in plastic bags up to 10 days, then fixed in formalin for 2–5 days before processing; or 3) exposed to room air and temperature for 1–5 days before formalin fixation. Immunohistochemical staining intensity was evaluated without the knowledge of specimen handling. Staining of specimens that had been promptly fixed in formalin was moderate to strong at all fixation periods through 36 days, weak or no staining was evident in specimens fixed for 176 days. Refrigerated specimens typically had moderate to strong immunohistochemical staining. Even after 10 days of refrigeration before fixation, all immunohistochemical reactions were positive. However, no immunohistochemical staining was detected in any specimen that was exposed to room air. Results indicate that prompt formalin fixation is optimal for BVDV IHC. Samples can be held in formalin at least 36 days, without loss of reactivity. A 1-day delay in fixation caused no loss of reactivity, provided the specimen was refrigerated and protected from desiccation.


Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2431
Author(s):  
Yusuke Goto ◽  
Gakuji Yaegashi ◽  
Kazuhiro Fukunari ◽  
Tohru Suzuki

Bovine viral diarrhea virus (BVDV) infection results in a wide variety of clinical manifestations and is a pathogen that is able to cause huge economic losses in the cattle industry worldwide. It is important to identify cattle that are persistently infected (PI) by BVDV within the herd as early as possible because PI animals are the main reservoir of the virus. In contrast, cattle who are acutely infected (AI) with BVDV show various clinical signs, but most cattle show either mild symptoms or are asymptomatic. In general, AI and PI animals can be distinguished by repeat testing within an interval of at least 21 days. However, we found a rare case of a BVDV2-infected AI animal with long-term viral presence, making it indistinguishable from PI through two tests within an interval of 21 days. As a result, we diagnosed one infected animal as AI after 35 days from the initial sample collection via multiple analyses. Our findings recommend performing an additional test using samples that have been collected after 14–21 days from the second sample collection in cases where it is difficult to accurately differentiate an AI diagnosis from a PI diagnosis after only two tests. Additionally, our analysis exhibits that monitoring the number of copies of viruses with similar genomes in the sera by means of quantitative real-time RT-PCR through several sample collections periods might be useful to distinguish AI from PI. Furthermore, our data suggest that the AI animals with a long-term viral presence who show test results similar to those of PI animals might be the result of a coincidental combination of various factors that are present in cattle fields. These findings provide useful information that can be used to improve the diagnosis of BVDV in the field.


2009 ◽  
Vol 29 (1) ◽  
pp. 23-36 ◽  
Author(s):  
Megan L. Shoemaker ◽  
Natalia P. Smirnova ◽  
Helle Bielefeldt-Ohmann ◽  
Kathleen J. Austin ◽  
Alberto van Olphen ◽  
...  

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