Special Issue "Bovine Viral Diarrhea Virus and Related Pestiviruses"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 May 2020).

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A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Helle Bielefeldt-Ohmann
E-Mail Website
Guest Editor
1. Infectious Diseases Research Centre, The University of Queensland, St. Lucia, QLD 4072, Australia
2. School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
3. School of Veterinary Medicine, The University of Queensland, Gatton Campus, QLD 4343, Australia.
Interests: infectious diseases pathobiology; viral persistence; flaviviruses; transplacental virus infections; co-infections; viral zoonoses; arbo-viruses; influenza viruses
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Special Issue Information

Dear Colleagues,

The genus Pestivirus, encompassing small positive-strand RNA viruses in the family Flaviviridae, comprises four viruses of very significant economic impact to the cattle, swine and sheep industries: bovine viral diarrhea virus (BVDV)-1 and -2, classical swine fever virus (CSFV) and border disease virus (BDV). In addition, a number of novel viruses have been detected in wild and domestic animals by isolation and/or virome studies, which appear to be related to the pestiviruses and may qualify as new pestivirus species. In this Issue, we would like to focus on studies aiming at establishing the pathogenesis of the pestiviruses and candidate pestiviruses, including transplacental infections and virus persistence. Research studies can also be focused on the epidemiology, development and evaluation of diagnostic assays, virus discovery, transmission pathways, virulence, clinical aspects and vaccines.

Dr. Helle Bielefeldt-Ohmann
Guest Editor

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Keywords

  • pestivirus
  • bovine viral diarrhea virus
  • mucosal disease
  • classical swine fever virus
  • border disease virus
  • pathogenesis
  • viral persistence
  • transplacental infection

Published Papers (21 papers)

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Editorial

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Editorial
Special Issue: Bovine Viral Diarrhea Virus and Related Pestiviruses
Viruses 2020, 12(10), 1181; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101181 - 19 Oct 2020
Cited by 2 | Viewed by 865
Abstract
The genus Pestivirus, encompassing small positive-strand RNA viruses in the family Flaviviridae, comprises four viruses of very significant economic impact to the cattle, swine and sheep industries worldwide: bovine viral diarrhoea virus (BVDV) type 1 and type 2, classical swine fever [...] Read more.
The genus Pestivirus, encompassing small positive-strand RNA viruses in the family Flaviviridae, comprises four viruses of very significant economic impact to the cattle, swine and sheep industries worldwide: bovine viral diarrhoea virus (BVDV) type 1 and type 2, classical swine fever virus (CSFV) and border disease virus (BDV) [...] Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)

Research

Jump to: Editorial, Review, Other

Article
Atypical Porcine Pestivirus Circulation and Molecular Evolution within an Affected Swine Herd
Viruses 2020, 12(10), 1080; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101080 - 25 Sep 2020
Cited by 6 | Viewed by 900
Abstract
Atypical porcine pestivirus (APPV) is a single-stranded RNA virus from the family Flaviviridae, which is linked to congenital tremor (CT) type A-II in newborn piglets. Here, we retrospectively investigated the molecular evolution of APPV on an affected herd between 2013 and 2019. Monitoring [...] Read more.
Atypical porcine pestivirus (APPV) is a single-stranded RNA virus from the family Flaviviridae, which is linked to congenital tremor (CT) type A-II in newborn piglets. Here, we retrospectively investigated the molecular evolution of APPV on an affected herd between 2013 and 2019. Monitoring was done at regular intervals, and the same genotype of APPV was found during the entire study period, suggesting no introductions from outside the farm. The nucleotide substitutions over time did not show substantial amino acid variation in the structural glycoproteins. Furthermore, the evolution of the virus showed mainly purifying selection, and no positive selection. The limited pressure on the virus to change at immune-dominant regions suggested that the immune pressure at the farm might be low. In conclusion, farms can have circulation of APPV for years, and massive testing and removal of infected animals are not sufficient to clear the virus from affected farms. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Article
The Outcome of Porcine Foetal Infection with Bungowannah Virus Is Dependent on the Stage of Gestation at Which Infection Occurs. Part 2: Clinical Signs and Gross Pathology
Viruses 2020, 12(8), 873; https://0-doi-org.brum.beds.ac.uk/10.3390/v12080873 - 10 Aug 2020
Cited by 1 | Viewed by 879
Abstract
Bungowannah virus is a novel pestivirus identified from a disease outbreak in a piggery in Australia in June 2003. The aim of this study was to determine whether infection of pregnant pigs with Bungowannah virus induces the clinical signs and gross pathology observed [...] Read more.
Bungowannah virus is a novel pestivirus identified from a disease outbreak in a piggery in Australia in June 2003. The aim of this study was to determine whether infection of pregnant pigs with Bungowannah virus induces the clinical signs and gross pathology observed during the initial outbreak and how this correlates with the time of infection. Twenty-four pregnant pigs were infected at one of four stages of gestation (approximately 35, 55, 75 or 90 days). The number of progeny born alive, stillborn or mummified, and signs of disease were recorded. Some surviving piglets were euthanased at weaning and others at ages up to 11 months. All piglets were subjected to a detailed necropsy. The greatest effects were observed following infection at 35 or 90 days of gestation. Infection at 35 days resulted in a significant reduction in the number of pigs born alive and an increased number of mummified foetuses (18%) and preweaning mortalities (70%). Preweaning losses were higher following infection at 90 days of gestation (29%) and were associated with sudden death and cardiorespiratory signs. Stunting occurred in chronically and persistently infected animals. This study reproduced the clinical signs and gross pathology of the porcine myocarditis syndrome and characterised the association between the time of infection and the clinical outcome. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Article
A CRISPR/Cas9 Generated Bovine CD46-knockout Cell Line—A Tool to Elucidate the Adaptability of Bovine Viral Diarrhea Viruses (BVDV)
Viruses 2020, 12(8), 859; https://0-doi-org.brum.beds.ac.uk/10.3390/v12080859 - 06 Aug 2020
Cited by 5 | Viewed by 1587
Abstract
Bovine viral diarrhea virus (BVDV) entry into a host cell is mediated by the interaction of the viral glycoprotein E2 with the cellular transmembrane CD46 receptor. In this study, we generated a stable Madin–Darby Bovine Kidney (MDBK) CD46-knockout cell line to study the [...] Read more.
Bovine viral diarrhea virus (BVDV) entry into a host cell is mediated by the interaction of the viral glycoprotein E2 with the cellular transmembrane CD46 receptor. In this study, we generated a stable Madin–Darby Bovine Kidney (MDBK) CD46-knockout cell line to study the ability of different pestivirus A and B species (BVDV-1 and -2) to escape CD46-dependent cell entry. Four different BVDV-1/2 isolates showed a clearly reduced infection rate after inoculation of the knockout cells. However, after further passaging starting from the remaining virus foci on the knockout cell line, all tested virus isolates were able to escape CD46-dependency and grew despite the lack of the entry receptor. Whole-genome sequencing of the escape-isolates suggests that the genetic basis for the observed shift in infectivity is an amino acid substitution of an uncharged (glycine/asparagine) for a charged amino acid (arginine/lysine) at position 479 in the ERNS in three of the four isolates tested. In the fourth isolate, the exchange of a cysteine at position 441 in the ERNS resulted in a loss of ERNS dimerization that is likely to influence viral cell-to-cell spread. In general, the CD46-knockout cell line is a useful tool to analyze the role of CD46 for pestivirus replication and the virus–receptor interaction. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Article
Fetal Lymphoid Organ Immune Responses to Transient and Persistent Infection with Bovine Viral Diarrhea Virus
Viruses 2020, 12(8), 816; https://0-doi-org.brum.beds.ac.uk/10.3390/v12080816 - 28 Jul 2020
Cited by 6 | Viewed by 1066
Abstract
Bovine Viral Diarrhea Virus (BVDV) fetal infections occur in two forms; persistent infection (PI) or transient infection (TI), depending on what stage of gestation the fetus is infected. Examination of lymphoid organs from both PI and TI fetuses reveals drastically different fetal responses, [...] Read more.
Bovine Viral Diarrhea Virus (BVDV) fetal infections occur in two forms; persistent infection (PI) or transient infection (TI), depending on what stage of gestation the fetus is infected. Examination of lymphoid organs from both PI and TI fetuses reveals drastically different fetal responses, dependent upon the developmental stage of the fetal immune system. Total RNA was extracted from the thymuses and spleens of uninfected control, PI, and TI fetuses collected on day 190 of gestation to test the hypothesis that BVDV infection impairs the innate and adaptive immune response in the fetal thymus and spleen of both infection types. Transcripts of genes representing the innate immune response and adaptive immune response genes were assayed by Reverse Transcription quatitative PCR (RT-qPCR) (2−ΔΔCq; fold change). Genes of the innate immune response, interferon (IFN) inducible genes, antigen presentation to lymphocytes, and activation of B cells were downregulated in day 190 fetal PI thymuses compared to controls. In contrast, innate immune response genes were upregulated in TI fetal thymuses compared to controls and tended to be upregulated in TI fetal spleens. Genes associated with the innate immune system were not different in PI fetal spleens; however, adaptive immune system genes were downregulated, indicating that PI fetal BVDV infection has profound inhibitory effects on the expression of genes involved in the innate and adaptive immune response. The downregulation of these genes in lymphocytes and antigen-presenting cells in the developing thymus and spleen may explain the incomplete clearance of BVDV and the persistence of the virus in PI animals while the upregulation of the TI innate immune response indicates a more mature immune system, able to clear the virus. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Article
An Assessment of Secondary Clinical Disease, Milk Production and Quality, and the Impact on Reproduction in Holstein Heifers and Cows from a Single Large Commercial Herd Persistently Infected with Bovine Viral Diarrhea Virus Type 2
Viruses 2020, 12(7), 760; https://0-doi-org.brum.beds.ac.uk/10.3390/v12070760 - 15 Jul 2020
Cited by 3 | Viewed by 1115
Abstract
The aim of this study was to evaluate secondary clinical disease, milk production efficiency and reproductive performance of heifers and cows persistently infected (PI) with bovine viral diarrhea virus type 2 (BVDV type 2). PI animals (n = 25) were identified using [...] Read more.
The aim of this study was to evaluate secondary clinical disease, milk production efficiency and reproductive performance of heifers and cows persistently infected (PI) with bovine viral diarrhea virus type 2 (BVDV type 2). PI animals (n = 25) were identified using an antigen capture ELISA of ear notch samples. They were distributed into three age groups: ≤ 12 (n = 8), 13 to 24 (n = 6) and 25 to 34 (n = 11) months old. A control group of BVDV antigen ELISA negative female cattle that were age matched to the PI animals was utilized from the same herd. The PI group had a 1.29 higher odds ratio for diarrhea than controls (p = 0.001, IC95% = 1.032–1.623) and 1.615 greater chance of developing bovine respiratory disease (BRD) (p = 0.012, IC95% = 1.155–2.259). The age at first insemination (p = 0.012) and number of insemination attempts required to establish the first pregnancy (p = 0.016) were both higher for PI than controls. Milk production was higher for control cows than PI cows during most of the sampling periods. Somatic cell counts (SCC) were higher in PI cows than the controls at all sampling points across lactation (p ≤ 0.042). PI cattle had a higher incidence of disease, produced less milk, a higher SCC, and poorer reproductive performance than control cattle in this study. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Article
Serosurveillance and Molecular Investigation of Wild Deer in Australia Reveals Seroprevalence of Pestivirus Infection
Viruses 2020, 12(7), 752; https://0-doi-org.brum.beds.ac.uk/10.3390/v12070752 - 13 Jul 2020
Cited by 6 | Viewed by 1510
Abstract
Since deer were introduced into Australia in the mid-1800s, their wild populations have increased in size and distribution, posing a potential risk to the livestock industry, through their role in pathogen transmission cycles. In comparison to livestock, there are limited data on viral [...] Read more.
Since deer were introduced into Australia in the mid-1800s, their wild populations have increased in size and distribution, posing a potential risk to the livestock industry, through their role in pathogen transmission cycles. In comparison to livestock, there are limited data on viral infections in all wildlife, including deer. The aim of this study was to assess blood samples from wild Australian deer for serological evidence of exposure to relevant viral livestock diseases. Blood samples collected across eastern Australia were tested by ELISA to detect antigens and antibodies against Pestivirus and antibodies against bovine herpesvirus 1. A subset of samples was also assessed by RT-PCR for Pestivirus, Simbu serogroup, epizootic hemorrhagic disease virus and bovine ephemeral fever virus. Our findings demonstrated a very low seroprevalence (3%) for ruminant Pestivirus, and none of the other viruses tested were detected. These results suggest that wild deer may currently be an incidental spill-over host (rather than a reservoir host) for Pestivirus. However, deer could be a future source of viral infections for domestic animals in Australia. Further investigations are needed to monitor pathogen activity and quantify possible future infectious disease impacts of wild deer on the Australian livestock industry. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Article
The Effect of Bovine Viral Diarrhea Virus (BVDV) Strains and the Corresponding Infected-Macrophages’ Supernatant on Macrophage Inflammatory Function and Lymphocyte Apoptosis
Viruses 2020, 12(7), 701; https://0-doi-org.brum.beds.ac.uk/10.3390/v12070701 - 29 Jun 2020
Cited by 3 | Viewed by 1175
Abstract
Bovine viral diarrhea virus (BVDV) is an important viral disease of cattle that causes immune dysfunction. Macrophages are the key cells for the initiation of the innate immunity and play an important role in viral pathogenesis. In this in vitro study, we studied [...] Read more.
Bovine viral diarrhea virus (BVDV) is an important viral disease of cattle that causes immune dysfunction. Macrophages are the key cells for the initiation of the innate immunity and play an important role in viral pathogenesis. In this in vitro study, we studied the effect of the supernatant of BVDV-infected macrophage on immune dysfunction. We infected bovine monocyte-derived macrophages (MDM) with high or low virulence strains of BVDV. The supernatant recovered from BVDV-infected MDM was used to examine the functional activity and surface marker expression of normal macrophages as well as lymphocyte apoptosis. Supernatants from the highly virulent 1373-infected MDM reduced phagocytosis, bactericidal activity and downregulated MHC II and CD14 expression of macrophages. Supernatants from 1373-infected MDM induced apoptosis in MDBK cells, lymphocytes or BL-3 cells. By protein electrophoresis, several protein bands were unique for high-virulence, 1373-infected MDM supernatant. There was no significant difference in the apoptosis-related cytokine mRNA (IL-1beta, IL-6 and TNF-a) of infected MDM. These data suggest that BVDV has an indirect negative effect on macrophage functions that is strain-specific. Further studies are required to determine the identity and mechanism of action of these virulence factors present in the supernatant of the infected macrophages. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Article
The Outcome of Porcine Foetal Infection with Bungowannah Virus Is Dependent on the Stage of Gestation at Which Infection Occurs. Part 1: Serology and Virology
Viruses 2020, 12(6), 691; https://0-doi-org.brum.beds.ac.uk/10.3390/v12060691 - 26 Jun 2020
Cited by 5 | Viewed by 788
Abstract
Bungowannah virus is a novel porcine pestivirus identified in a disease outbreak in Australia in 2003. The aim of this study was to determine the outcome of infection of the pregnant pig with this virus. Twenty-four pregnant pigs were infected at days 35, [...] Read more.
Bungowannah virus is a novel porcine pestivirus identified in a disease outbreak in Australia in 2003. The aim of this study was to determine the outcome of infection of the pregnant pig with this virus. Twenty-four pregnant pigs were infected at days 35, 55, 75 or 90 of gestation. Blood, tonsillar and rectal swabs were collected from each pig at birth and then weekly until euthanasia or death. Tissues were sampled at necropsy. Viral load was measured by real-time reverse-transcription polymerase chain reaction (qRT-PCR) and antibody levels in serum by peroxidase-linked immunoassay. Bungowannah virus was detected in the serum and excretions of all infected pigs at birth regardless of the stage of gestation at which infection occurred. Persistent infections occurred following infection prior to the development of foetal immunocompetence. Unexpectedly some animals infected at day 55 of gestation later cleared the virus and seroconverted. Viraemia and viral shedding resolved quickest following infection in late gestation. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Article
Infection of Ruminants, Including Pregnant Cattle, with Bungowannah Virus
Viruses 2020, 12(6), 690; https://0-doi-org.brum.beds.ac.uk/10.3390/v12060690 - 26 Jun 2020
Cited by 1 | Viewed by 836
Abstract
Bungowannah virus is a pestivirus known to cause reproductive losses in pigs. The virus has not been found in other species, nor is it known if it has the capacity to cause disease in other animals. Eight sheep, eight calves and seven pregnant [...] Read more.
Bungowannah virus is a pestivirus known to cause reproductive losses in pigs. The virus has not been found in other species, nor is it known if it has the capacity to cause disease in other animals. Eight sheep, eight calves and seven pregnant cows were experimentally infected with Bungowannah virus. It was found that sheep and calves could be infected. Furthermore, it was shown that the virus is able to cross the bovine placenta and cause infection of the foetus. These findings demonstrate the potential for species other than pigs to become infected with Bungowannah virus and the need to prevent them from becoming infected. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
Article
Prevalence and Genetic Diversity of Atypical Porcine Pestivirus (APPV) Detected in South Korean Wild Boars
Viruses 2020, 12(6), 680; https://0-doi-org.brum.beds.ac.uk/10.3390/v12060680 - 24 Jun 2020
Cited by 10 | Viewed by 975
Abstract
Atypical porcine pestivirus (APPV), currently classified as pestivirus K, causes congenital tremor (CT) type A-II in piglets. Eighteen APPV strains were identified from 2297 South Korean wild boars captured in 2019. Phylogenetic analysis of the structural protein E2 and nonstructural proteins NS3 [...] Read more.
Atypical porcine pestivirus (APPV), currently classified as pestivirus K, causes congenital tremor (CT) type A-II in piglets. Eighteen APPV strains were identified from 2297 South Korean wild boars captured in 2019. Phylogenetic analysis of the structural protein E2 and nonstructural proteins NS3 and Npro classified the APPV viruses, including reference strains, into Clades I, II and III. Clade I was divided into four subclades; however, the strains belonging to the four subclades differed slightly, depending on the tree analysis, the NS3, E2, and Npro genes. The maximum-likelihood method was assigned to South Korean wild boar APPV strains to various subclades within the three trees: subclades I.1 and I.2 in the E2 tree, subclade I.1 in the Npro tree, and subclades I.1 and I.4 in the NS3 ML tree. In conclusion, APPV among South Korean wild boars belonging to Clade I may be circulating at a higher level than among the South Korean domestic pig populations. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Article
Prolonged Detection of Bovine Viral Diarrhoea Virus Infection in the Semen of Bulls
Viruses 2020, 12(6), 674; https://0-doi-org.brum.beds.ac.uk/10.3390/v12060674 - 22 Jun 2020
Cited by 8 | Viewed by 1302
Abstract
Infection of bulls with bovine viral diarrhoea virus (BVDV) can result in the development of virus persistence, confined to the reproductive tract. These bulls develop a normal immune response with high neutralizing antibody titres. However, BVDV can be excreted in the semen for [...] Read more.
Infection of bulls with bovine viral diarrhoea virus (BVDV) can result in the development of virus persistence, confined to the reproductive tract. These bulls develop a normal immune response with high neutralizing antibody titres. However, BVDV can be excreted in the semen for a prolonged period. Although relatively rare, in this study we describe six separate cases in bulls being prepared for admission to artificial breeding centres. Semen samples were tested in a pan-Pestivirus-reactive real-time PCR assay and viral RNA was detected in semen from five of the bulls for three to eight months after infection. In one bull, virus was detected at low levels for more than five years. This bull was found to have one small testis. When slaughtered, virus was only detected in the abnormal testis. The low levels of BVDV in the semen of these bulls were only intermittently detected by virus isolation in cell culture. This virus-contaminated semen presents a biosecurity risk and confirms the need to screen all batches of semen from bulls that have been previously infected with BVDV. The use of real-time PCR is recommended as the preferred laboratory assay for this purpose. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Article
Real Time Analysis of Bovine Viral Diarrhea Virus (BVDV) Infection and Its Dependence on Bovine CD46
Viruses 2020, 12(1), 116; https://0-doi-org.brum.beds.ac.uk/10.3390/v12010116 - 17 Jan 2020
Cited by 5 | Viewed by 1753
Abstract
Virus attachment and entry is a complex interplay of viral and cellular interaction partners. Employing bovine viral diarrhea virus (BVDV) encoding an mCherry-E2 fusion protein (BVDVE2-mCherry), being the first genetically labelled member of the family Flaviviridae applicable for the analysis of [...] Read more.
Virus attachment and entry is a complex interplay of viral and cellular interaction partners. Employing bovine viral diarrhea virus (BVDV) encoding an mCherry-E2 fusion protein (BVDVE2-mCherry), being the first genetically labelled member of the family Flaviviridae applicable for the analysis of virus particles, the early events of infection—attachment, particle surface transport, and endocytosis—were monitored to better understand the mechanisms underlying virus entry and their dependence on the virus receptor, bovine CD46. The analysis of 801 tracks on the surface of SK6 cells inducibly expressing fluorophore labelled bovine CD46 (CD46fluo) demonstrated the presence of directed, diffusive, and confined motion. 26 entry events could be identified, with the majority being associated with a CD46fluo positive structure during endocytosis and occurring more than 20 min after virus addition. Deletion of the CD46fluo E2 binding domain (CD46fluo∆E2bind) did not affect the types of motions observed on the cell surface but resulted in a decreased number of observable entry events (2 out of 1081 tracks). Mean squared displacement analysis revealed a significantly increased velocity of particle transport for directed motions on CD46fluo∆E2bind expressing cells in comparison to CD46fluo. These results indicate that the presence of bovine CD46 is only affecting the speed of directed transport, but otherwise not influencing BVDV cell surface motility. Instead, bovine CD46 seems to be an important factor during uptake, suggesting the presence of additional cellular proteins interacting with the virus which are able to support its transport on the virus surface. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Article
Pestivirus Infections in Semi-Domesticated Eurasian Tundra Reindeer (Rangifer tarandus tarandus): A Retrospective Cross-Sectional Serological Study in Finnmark County, Norway
Viruses 2020, 12(1), 29; https://0-doi-org.brum.beds.ac.uk/10.3390/v12010029 - 26 Dec 2019
Cited by 3 | Viewed by 1238
Abstract
Members of the Pestivirus genus (family Flaviviridae) cause severe and economically important diseases in livestock. Serological studies have revealed the presence of pestiviruses in different cervid species, including wild and semi-domesticated Eurasian tundra reindeer. In this retrospective study, serum samples collected between [...] Read more.
Members of the Pestivirus genus (family Flaviviridae) cause severe and economically important diseases in livestock. Serological studies have revealed the presence of pestiviruses in different cervid species, including wild and semi-domesticated Eurasian tundra reindeer. In this retrospective study, serum samples collected between 2006 and 2008 from 3339 semi-domesticated Eurasian reindeer from Finnmark County, Norway, were tested for anti-pestivirus antibodies using an enzyme linked immunosorbent assay (ELISA) and a subset of these by virus neutralization test (VNT). A seroprevalence of 12.5% was found, varying from 0% to 45% among different herding districts, and 20% in western Finnmark, as compared to 1.7% in eastern Finnmark. Seroprevalence increased with age. Pestivirus-specific RNA was not detected in any of the 225 serum samples tested by real-time RT-PCR. Based on VNT results, using a panel of one bovine viral diarrhea virus (BVDV) strain and two border disease virus (BDV) strains, the virus is most likely a reindeer-specific pestivirus closely related to BDV. A characterization of the causative virus and its pathogenic impact on reindeer populations, as well as its potential to infect other domestic and wild ruminants, should be further investigated. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Article
Molecular Survey and Phylogenetic Analysis of Atypical Porcine Pestivirus (APPV) Identified in Swine and Wild Boar from Northern Italy
Viruses 2019, 11(12), 1142; https://0-doi-org.brum.beds.ac.uk/10.3390/v11121142 - 10 Dec 2019
Cited by 12 | Viewed by 1093
Abstract
Atypical porcine pestivirus (APPV) is a newly recognized member of the Flaviviridae family. This novel porcine pestivirus was first described in 2015 in the USA, where it has been associated with congenital tremor type A-II in new-born piglets. APPV is widely distributed in [...] Read more.
Atypical porcine pestivirus (APPV) is a newly recognized member of the Flaviviridae family. This novel porcine pestivirus was first described in 2015 in the USA, where it has been associated with congenital tremor type A-II in new-born piglets. APPV is widely distributed in domestic pigs in Europe and Asia. In this study, a virological survey was performed in Northern Italy to investigate the presence of APPV using molecular methods. Testing of 360 abortion samples from pig herds revealed two APPV strains from distinct provinces in the Lombardy region and testing of 430 wild boar blood samples revealed three strains, one from Lombardy and two from Emilia Romagna. The nucleotide sequencing of a fragment of the nonstructural protein 3-coding region revealed a high similarity to the previously detected European strains (Spanish, German, and Italian) of APPV. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Article
Clinical and Serological Evaluation of LINDA Virus Infections in Post-Weaning Piglets
Viruses 2019, 11(11), 975; https://0-doi-org.brum.beds.ac.uk/10.3390/v11110975 - 23 Oct 2019
Cited by 4 | Viewed by 1212
Abstract
The novel pestivirus species known as lateral-shaking inducing neuro-degenerative agent (LINDA) virus emerged in 2015 in a piglet-producing farm in Austria. Affected piglets showed strong congenital tremor as a result of severe lesions in the central nervous system. Here, we report the results [...] Read more.
The novel pestivirus species known as lateral-shaking inducing neuro-degenerative agent (LINDA) virus emerged in 2015 in a piglet-producing farm in Austria. Affected piglets showed strong congenital tremor as a result of severe lesions in the central nervous system. Here, we report the results of a controlled animal infection experiment. Post-weaning piglets were infected with LINDA to determine the susceptibility of pigs, the clinical consequences of infection and the humoral immune response against LINDA. No clinically overt disease signs were observed in the piglets. Viremia was hardly detectable, but LINDA was present in the spleen and several lymphatic organs until the end of the experiment on day 28 post-infection. Oronasal virus shedding together with the infection of one sentinel animal provided additional evidence for the successful replication and spread of LINDA in the piglets. Starting on day 14 post-infection, all infected animals showed a strong humoral immune response with high titers of neutralizing antibodies against LINDA. No cross-neutralizing activity of these sera with other pestiviral species was observed. According to these data, following postnatal infection, LINDA is a rather benign virus that can be controlled by the pig’s immune system. However, further studies are needed to investigate the effects of LINDA on the fetus after intrauterine infection. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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Review

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Review
Bovine Pestivirus Heterogeneity and Its Potential Impact on Vaccination and Diagnosis
Viruses 2020, 12(10), 1134; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101134 - 06 Oct 2020
Cited by 11 | Viewed by 1231
Abstract
Bovine Pestiviruses A and B, formerly known as bovine viral diarrhoea viruses (BVDV)-1 and 2, respectively, are important pathogens of cattle worldwide, responsible for significant economic losses. Bovine viral diarrhoea control programmes are in effect in several high-income countries but less so in [...] Read more.
Bovine Pestiviruses A and B, formerly known as bovine viral diarrhoea viruses (BVDV)-1 and 2, respectively, are important pathogens of cattle worldwide, responsible for significant economic losses. Bovine viral diarrhoea control programmes are in effect in several high-income countries but less so in low- and middle-income countries where bovine pestiviruses are not considered in disease control programmes. However, bovine pestiviruses are genetically and antigenically diverse, which affects the efficiency of the control programmes. The emergence of atypical ruminant pestiviruses (Pestivirus H or BVDV-3) from various parts of the world and the detection of Pestivirus D (border disease virus) in cattle highlights the challenge that pestiviruses continue to pose to control measures including the development of vaccines with improved cross-protective potential and enhanced diagnostics. This review examines the effect of bovine pestivirus diversity and emergence of atypical pestiviruses in disease control by vaccination and diagnosis. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
Review
Epidemiology and Management of BVDV in Rangeland Beef Breeding Herds in Northern Australia
Viruses 2020, 12(10), 1063; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101063 - 23 Sep 2020
Cited by 1 | Viewed by 901
Abstract
Approximately 60% of Australia’s beef cattle are located in the vast rangelands of northern Australia. Despite the often low stocking densities and extensive management practices of the observed herd, animal prevalence of BVDV infection and typical rates of transmission are similar to those [...] Read more.
Approximately 60% of Australia’s beef cattle are located in the vast rangelands of northern Australia. Despite the often low stocking densities and extensive management practices of the observed herd, animal prevalence of BVDV infection and typical rates of transmission are similar to those observed in intensively managed herds in southern Australia and elsewhere in the world. A recent large three- to four-year study of factors affecting the reproductive performance of breeding herds in this region found that where there was evidence of widespread and/or recent BVDV infection, the percentage of lactating cows that became pregnant within four months of calving was reduced by 23%, and calf wastage was increased by 9%. BVDV is now considered the second most important endemic disease affecting beef cattle in northern Australia, costing the industry an estimated AUD 50.9 million annually. Although an effective killed vaccine was released in Australia in 2003, the adoption of routine whole herd vaccination by commercial beef farmers has been slow. However, routine testing to identify persistently infected replacement breeding bulls and heifers has been more widely adopted. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
Review
Pestivirus K (Atypical Porcine Pestivirus): Update on the Virus, Viral Infection, and the Association with Congenital Tremor in Newborn Piglets
Viruses 2020, 12(8), 903; https://0-doi-org.brum.beds.ac.uk/10.3390/v12080903 - 18 Aug 2020
Cited by 5 | Viewed by 1164
Abstract
The atypical porcine pestivirus (APPV) belongs to the species Pestivirus K of the genus Pestivirus and the family Flaviviridae, and it has been associated with congenital tremor (CT) type A-II in newborn piglets. Although APPV was discovered in 2015, evidence shows that [...] Read more.
The atypical porcine pestivirus (APPV) belongs to the species Pestivirus K of the genus Pestivirus and the family Flaviviridae, and it has been associated with congenital tremor (CT) type A-II in newborn piglets. Although APPV was discovered in 2015, evidence shows that APPV has circulated in pig herds for many years, at least since 1986. Due to the frequently reported outbreaks of CT on different continents, the importance of this virus for global pig production is notable. Since 2015, several studies have been conducted to clarify the association between APPV and CT. However, some findings regarding APPV infection and the measures taken to control and prevent the spread of this virus need to be contextualized to understand the infection better. This review attempts to highlight advances in the understanding of APPV associated with type A-II CT, such as etiology, epidemiology, diagnosis, and control and prevention measures, and also describes the pathophysiology of the infection and its consequences for pig production. Further research still needs to be conducted to elucidate the host’s immune response to APPV infection, the control and prevention of this infection, and the possible development of vaccines. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
Review
Bovine Viral Diarrhea Virus: Recent Findings about Its Occurrence in Pigs
Viruses 2020, 12(6), 600; https://0-doi-org.brum.beds.ac.uk/10.3390/v12060600 - 31 May 2020
Cited by 8 | Viewed by 1291
Abstract
Bovine viral diarrhea virus (BVDV) is an important pathogen belonging to the Pestivirus genus, Flaviviridae family, which comprises viral species that causes an economic impact in animal production. Cattle are the natural host of BVDV and the main source of infection for pigs [...] Read more.
Bovine viral diarrhea virus (BVDV) is an important pathogen belonging to the Pestivirus genus, Flaviviridae family, which comprises viral species that causes an economic impact in animal production. Cattle are the natural host of BVDV and the main source of infection for pigs and other animal species. Due to its antigenic and genetic similarity with other important pestiviruses such as Classical Swine Fever Virus (CSFV), several studies have been conducted to elucidate the real role of this virus in piglets, sows, and boars, not only in the field but also in experimental infections, which will be discussed in this paper. Although BVDV does not pose a threat to pigs as it does to ruminants, the occurrence of clinical signs is variable and may depend on several factors. Therefore, this study presents a survey of data on BVDV infection in pigs, comparing information on prevalence in different countries and the results of experimental infections to understand this type of infection in pigs better. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)

Other

Brief Report
Single-Round Infectious Particle Production by DNA-Launched Infectious Clones of Bungowannah Pestivirus
Viruses 2020, 12(8), 847; https://0-doi-org.brum.beds.ac.uk/10.3390/v12080847 - 04 Aug 2020
Cited by 1 | Viewed by 1190
Abstract
Reverse genetics systems are powerful tools for functional studies of viral genes or for vaccine development. Here, we established DNA-launched reverse genetics for the pestivirus Bungowannah virus (BuPV), where cDNA flanked by a hammerhead ribozyme sequence at the 5′ end and the hepatitis [...] Read more.
Reverse genetics systems are powerful tools for functional studies of viral genes or for vaccine development. Here, we established DNA-launched reverse genetics for the pestivirus Bungowannah virus (BuPV), where cDNA flanked by a hammerhead ribozyme sequence at the 5′ end and the hepatitis delta ribozyme at the 3′ end was placed under the control of the CMV RNA polymerase II promoter. Infectious recombinant BuPV could be rescued from pBuPV-DNA-transfected SK-6 cells and it had very similar growth characteristics to BuPV generated by conventional RNA-based reverse genetics and wild type BuPV. Subsequently, DNA-based ERNS deleted BuPV split genomes (pBuPV∆ERNS/ERNS)—co-expressing the ERNS protein from a separate synthetic CAG promoter—were constructed and characterized in vitro. Overall, DNA-launched BuPV genomes enable a rapid and cost-effective generation of recombinant BuPV and virus mutants, however, the protein expression efficiency of the DNA-launched systems after transfection is very low and needs further optimization in the future to allow the use e.g., as vaccine platform. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Virus and Related Pestiviruses)
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