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Pestivirus 2024
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Pestivirus 2024

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

Deadline for manuscript submissions: 31 October 2024 | Viewed by 11188

Special Issue Editors

Prof. Dr. Benjamin J. Lamp

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Guest Editor
Institute of Virology, Faculty of Veterinary Medicine, Justus-Liebig-University Giessen, Schubertstrasse 81, 35392 Giessen, Germany
Interests: viral-related diseases of livestock and insects; plus-strand RNA viruses; deformed wing virus; sacbrood virus; chronic bee paralysis virus; picornavirales; dicistroviruses; reverse genetics
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Till Rümenapf

E-Mail Website
Guest Editor
Department of Pathobiology, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, Austria
Interests: pestiviruses; arteriviruses; persistent infections; cellular receptors
Prof. Dr. Christiane M. Riedel

E-Mail Website
Guest Editor
CIRI-Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, 46 Allee d'Italie, 69007 Lyon, France
Interests: pestiviruses; rhabdoviruses; Cryo EM; structural virology; virus entry, cellular receptors

Special Issue Information

Dear Colleagues,

Traditional pestiviruses, such as the classical swine fever virus or the bovine viral diarrhea virus, are known agents of economically important animal diseases. However, recent research has led to the identification of many different related viruses that also infect previously unknown host species, such as cetaceans, rodents, or pangolins. It is likely that this is only the tip of the iceberg and that additional pestivirus species will be discovered soon.

Moreover, the impact of new species on the health status of individual animals or entire populations and their implications for the conservation of endangered species are still unknown. Although we know much about immunomodulatory proteins, the establishment of persistent infections, and cellular host factors of pestiviruses, there have been recent breakthroughs in understanding the mechanisms of infection. Of particular note are the recent studies on cellular receptor molecules, of which ADAM17 has been identified as a major host factor and direct interactor of the envelope protein E2.

The aim of this Special Issue is to present and summarize the latest discoveries in basic research, as well as the developments and advances in the epidemiology, diagnostics, and control of pestiviruses. Emphasis is also placed on pestiviral diseases, their pathogenesis, and their economic or environmental importance. Further investigation into the newly discovered pestiviruses and the molecular infection mechanisms of the known species will continue to be an exciting and important area of research.

Prof. Dr. Benjamin J. Lamp
Prof. Dr. Till Rümenapf
Prof. Dr. Christiane M. Riedel
Guest Editors

Manuscript Submission Information

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Published Papers (10 papers)

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Research

13 pages, 4036 KiB  
Communication
Modulation of ADAM17 Levels by Pestiviruses Is Species-Specific
by Hann-Wei Chen, Marianne Zaruba, Aroosa Dawood, Stefan Düsterhöft, Benjamin Lamp, Till Ruemenapf and Christiane Riedel
Viruses 2024, 16(10), 1564; https://doi.org/10.3390/v16101564 - 2 Oct 2024
Viewed by 359
Abstract
Upon host cell infection, viruses modulate their host cells to better suit their needs, including the downregulation of virus entry receptors. ADAM17, a cell surface sheddase, is an essential factor for infection of bovine cells with several pestiviruses. To assess the effect of [...] Read more.
Upon host cell infection, viruses modulate their host cells to better suit their needs, including the downregulation of virus entry receptors. ADAM17, a cell surface sheddase, is an essential factor for infection of bovine cells with several pestiviruses. To assess the effect of pestivirus infection on ADAM17, the amounts of cellular ADAM17 and its presence at the cell surface were determined. Mature ADAM17 levels were reduced upon infection with a cytopathic pestivirus bovis (bovine viral diarrhea virus, cpBVDV), pestivirus suis (classical swine fever virus, CSFV) or pestivirus giraffae (strain giraffe), but not negatively affected by pestivirus L (Linda virus, LindaV). A comparable reduction of ADAM17 surface levels, which represents the bioactive form, could be observed in the presence of E2 of BVDV and CSFV, but not LindaV or atypical porcine pestivirus (pestivirus scrofae) E2. Superinfection exclusion in BVDV infection is caused by at least two proteins, glycoprotein E2 and protease/helicase NS3. To evaluate whether the lowered ADAM17 levels could be involved in superinfection exclusion, persistently CSFV- or LindaV-infected cells were challenged with different pestiviruses. Persistently LindaV-infected cells were significantly more susceptible to cpBVDV infection than persistently CSFV-infected cells, whilst the other pestiviruses tested were not or only hardly able to infect the persistently infected cells. These results provide evidence of a pestivirus species-specific effect on ADAM17 levels and hints at the possibility of its involvement in superinfection exclusion. Full article
(This article belongs to the Special Issue Pestivirus 2024)
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13 pages, 1492 KiB  
Article
Detection and Genetic Characterization of Border Disease Virus (BDV) Isolated from a Persistently Infected Sheep in a Migratory Flock from Rajasthan State, Northwestern India
by Semmannan Kalaiyarasu, Katherukamem Rajukumar, Niranjan Mishra, Shashi Bhusan Sudhakar and Vijendra Pal Singh
Viruses 2024, 16(9), 1390; https://doi.org/10.3390/v16091390 - 30 Aug 2024
Viewed by 638
Abstract
Border disease virus (BDV) causes significant economic losses in sheep farming worldwide. In India, BDV has not yet been studied in sheep migrating for summer pasturing. This study aimed to determine the extent of BDV infection in migratory sheep and provide genetic characteristics [...] Read more.
Border disease virus (BDV) causes significant economic losses in sheep farming worldwide. In India, BDV has not yet been studied in sheep migrating for summer pasturing. This study aimed to determine the extent of BDV infection in migratory sheep and provide genetic characteristics of BDV. Blood and serum samples from 90 lambs of a migratory sheep flock (600) in Central India were collected and subjected to molecular detection, phylogenetic analysis and virus neutralization test (VNT). We detected BDV in two lambs through real-time RT-PCR, while 64.4% (58/90) of in-contact lambs had BDV neutralizing antibodies. One apparently healthy lamb was found to be persistently infected with BDV. Phylogenetic analysis of 5′-UTR and Npro genes and the concatenated datasets typed the BDV isolate from PI sheep as BDV-3 genotype. However, it showed a closer relationship with BDV-3 strains from China than the previously reported Indian BDV-3 strains. This is the first report on the detection of BDV persistently infected migratory sheep in India. Additionally, we provided evidence of genetic variability among BDV-3 strains in India. The findings improve our understanding of epidemiology and genetic characteristics of BDV in India and highlight the potential risks associated with the traditional practice of sheep migration for summer pasturing. Full article
(This article belongs to the Special Issue Pestivirus 2024)
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19 pages, 10986 KiB  
Article
Bergamottin Inhibits Bovine Viral Diarrhea Virus Replication by Suppressing ROS-Mediated Endoplasmic Reticulum Stress and Apoptosis
by Jinhua Yin, Jialu Zhang, Yi Liu, Cong Duan and Jiufeng Wang
Viruses 2024, 16(8), 1287; https://doi.org/10.3390/v16081287 - 13 Aug 2024
Viewed by 763
Abstract
Bovine viral diarrhea virus (BVDV) is one of the most important etiological agents that causes serious economic losses to the global livestock industry. Vaccines usually provide limited efficacy against BVDV due to the emergence of mutant strains. Therefore, developing novel strategies to combat [...] Read more.
Bovine viral diarrhea virus (BVDV) is one of the most important etiological agents that causes serious economic losses to the global livestock industry. Vaccines usually provide limited efficacy against BVDV due to the emergence of mutant strains. Therefore, developing novel strategies to combat BVDV infection is urgently needed. Bergamottin (Berg), a natural furanocoumarin compound, possesses various pharmaceutical bioactivities, but its effect on BVDV infection remains unknown. The present study aimed to investigate the antiviral effect and underlying mechanism of Berg against BVDV infection. The results showed that Berg exhibited an inhibitory effect on BVDV replication in MDBK cells by disrupting the viral replication and release, rather than directly inactivating virus particles. Mechanistically, Berg inhibits BVDV replication by suppressing endoplasmic reticulum (ER) stress-mediated apoptosis via reducing reactive oxygen species (ROS) generation. Studies in vivo demonstrated that oral gavage of Berg at doses of 50 mg/kg and 75 mg/kg significantly reduced the viral load within the intestines and spleen in BVDV-challenged mice. Furthermore, histopathological damage and oxidative stress caused by BVDV were also mitigated with Berg treatment. Our data indicated that Berg suppressed BVDV propagation both in vitro and in vivo, suggesting it as a promising antiviral option against BVDV. Full article
(This article belongs to the Special Issue Pestivirus 2024)
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14 pages, 2827 KiB  
Article
Assessment of the Safety Profile of Chimeric Marker Vaccine against Classical Swine Fever: Reversion to Virulence Study
by Loc Tan Huynh, Mikihiro Otsuka, Maya Kobayashi, Hung Dinh Ngo, Lim Yik Hew, Takahiro Hiono, Norikazu Isoda and Yoshihiro Sakoda
Viruses 2024, 16(7), 1120; https://doi.org/10.3390/v16071120 - 12 Jul 2024
Viewed by 713
Abstract
Chimeric marker vaccine candidates, vGPE−/PAPeV Erns and vGPE−/PhoPeV Erns, have been generated and their efficacy and capability to differentiate infected from vaccinated animals were confirmed in previous studies. The safety profile of the two chimeric marker [...] Read more.
Chimeric marker vaccine candidates, vGPE−/PAPeV Erns and vGPE−/PhoPeV Erns, have been generated and their efficacy and capability to differentiate infected from vaccinated animals were confirmed in previous studies. The safety profile of the two chimeric marker vaccine candidates, particularly in the potential reversion to virulence, was evaluated. Each virus was administered to pigs with a dose equivalent to the vaccination dose, and pooled tonsil homogenates were subsequently inoculated into further pigs. Chimeric virus vGPE−/PAPeV Erns displayed the most substantial attenuation, achieving this within only two passages, whereas vGPE−/PhoPeV Erns was detectable until the third passage and disappeared entirely by the fourth passage. The vGPE− strain, assessed alongside, consistently exhibited stable virus recovery across each passage without any signs of increased virulence in pigs. In vitro assays revealed that the type I interferon-inducing capacity of vGPE−/PAPeV Erns was significantly higher than that of vGPE−/PhoPeV Erns and vGPE−. In conclusion, the safety profile of the two chimeric marker vaccine candidates was affirmed. Further research is essential to ensure the stability of their attenuation and safety in diverse pig populations. Full article
(This article belongs to the Special Issue Pestivirus 2024)
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16 pages, 2829 KiB  
Article
Safety and DIVA Capability of Novel Live Attenuated Classical Swine Fever Marker Vaccine Candidates in Pregnant Sows
by Chao Tong, Alice Mundt, Alexandra Meindl-Boehmer, Verena Haist, Andreas Gallei and Ning Chen
Viruses 2024, 16(7), 1043; https://doi.org/10.3390/v16071043 - 28 Jun 2024
Viewed by 957
Abstract
Classical Swine Fever (CSF), a highly contagious viral disease affecting pigs and wild boar, results in significant economic losses in the swine industry. In endemic regions, prophylactic vaccination and stamping-out strategies are used to control CSF outbreaks. However, sporadic outbreaks and persistent infections [...] Read more.
Classical Swine Fever (CSF), a highly contagious viral disease affecting pigs and wild boar, results in significant economic losses in the swine industry. In endemic regions, prophylactic vaccination and stamping-out strategies are used to control CSF outbreaks. However, sporadic outbreaks and persistent infections continue to be reported. Although the conventional attenuated CSF vaccines protect pigs against the disease, they do not allow for the differentiation of infected from vaccinated animals (DIVA), limiting their use as an eradication tool. In this study, three targeted attenuation strategies were employed to generate vaccine candidates based on the current prevalent CSFV group 2 strains GD18 and QZ07: a single deletion of H79 in Erns (QZ07-sdErnsH-KARD), double deletion of H79 and C171 in Erns (GD18-ddErnsHC-KARD and QZ07-ddErnsHC-KARD), and deletion of H79 in Erns combined with a 5–168 amino acids deletion of Npro (GD18-ddNpro-ErnsH-KARD). Additionally, a negative serological marker with four substitutions in a highly conserved epitope in E2 recognized by the monoclonal antibody 6B8 was introduced in each candidate for DIVA purposes. The safety of these four resulting vaccine candidates was evaluated in pregnant sows. Two candidates, GD18-ddErnsHC-KARD and QZ07-sdErnsH-KARD were found to be safe for pregnant sows and unlikely to cause vertical transmission. Both candidates also demonstrated potential to be used as DIVA vaccines, as was shown using a proprietary blocking ELISA based on the 6B8 monoclonal antibody. These results, together with our previous work, constitute a proof-of-concept for the rational design of CSF antigenically marked modified live virus vaccine candidates. Full article
(This article belongs to the Special Issue Pestivirus 2024)
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11 pages, 1102 KiB  
Article
Isolation and Molecular Evidence of Tunisian Sheep-like Pestivirus (Pestivirus N) in Persistently Infected Sheep in Northern Italy, 2023
by Enrica Sozzi, Gabriele Leo, Fatbardha Lamcja, Massimiliano Lazzaro, Cristian Salogni, Davide Lelli, Cristina Bertasio, Giulia Magagna, Ana Moreno, Giovanni Loris Alborali, Moira Bazzucchi and Antonio Lavazza
Viruses 2024, 16(6), 815; https://doi.org/10.3390/v16060815 - 21 May 2024
Viewed by 872
Abstract
Over the last few decades, several pestiviruses have been discovered in ruminants, pigs, and, more recently, in non-ungulate hosts. Consequently, the nomenclature and taxonomy of pestiviruses have been updated. The Tunisian sheep-like pestivirus (TSV, Pestivirus N) is an additional ovine pestivirus genetically [...] Read more.
Over the last few decades, several pestiviruses have been discovered in ruminants, pigs, and, more recently, in non-ungulate hosts. Consequently, the nomenclature and taxonomy of pestiviruses have been updated. The Tunisian sheep-like pestivirus (TSV, Pestivirus N) is an additional ovine pestivirus genetically closely related to classical swine fever virus (CSFV). In this study, during a survey of pestivirus infections in ovine farms in the Lombardy region of Northern Italy, we identified and isolated a pestivirus strain from a sheep that was found to belong to Pestivirus N species based on its genomic nucleotide identity. The sheep itself and its lamb were found to be persistently infected. We performed molecular characterization and phylogenetic analysis of three viral genomic regions (a fragment of 5′-UTR, partial Npro, and the whole E2 region). In conclusion, these results confirmed circulating TSV in Northern Italy after notification in Sicily, Italy, and France. Correlation with Italian, Tunisian, and French strains showed that detection might have resulted from the trading of live animals between countries, which supports the need for health control measures. Full article
(This article belongs to the Special Issue Pestivirus 2024)
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20 pages, 3218 KiB  
Article
Evolutionary-Related High- and Low-Virulent Classical Swine Fever Virus Isolates Reveal Viral Determinants of Virulence
by Yoandry Hinojosa, Matthias Liniger, Obdulio García-Nicolás, Markus Gerber, Anojen Rajaratnam, Sara Muñoz-González, Liani Coronado, María Teresa Frías, Carmen Laura Perera, Llilianne Ganges and Nicolas Ruggli
Viruses 2024, 16(1), 147; https://doi.org/10.3390/v16010147 - 19 Jan 2024
Viewed by 1454
Abstract
Classical swine fever (CSF) has been eradicated from Western and Central Europe but remains endemic in parts of Central and South America, Asia, and the Caribbean. CSF virus (CSFV) has been endemic in Cuba since 1993, most likely following an escape of the [...] Read more.
Classical swine fever (CSF) has been eradicated from Western and Central Europe but remains endemic in parts of Central and South America, Asia, and the Caribbean. CSF virus (CSFV) has been endemic in Cuba since 1993, most likely following an escape of the highly virulent Margarita/1958 strain. In recent years, chronic and persistent infections with low-virulent CSFV have been observed. Amino acid substitutions located in immunodominant epitopes of the envelope glycoprotein E2 of the attenuated isolates were attributed to positive selection due to suboptimal vaccination and control. To obtain a complete picture of the mutations involved in attenuation, we applied forward and reverse genetics using the evolutionary-related low-virulent CSFV/Pinar del Rio (CSF1058)/2010 (PdR) and highly virulent Margarita/1958 isolates. Sequence comparison of the two viruses recovered from experimental infections in pigs revealed 40 amino acid differences. Interestingly, the amino acid substitutions clustered in E2 and the NS5A and NS5B proteins. A long poly-uridine sequence was identified previously in the 3′ untranslated region (UTR) of PdR. We constructed functional cDNA clones of the PdR and Margarita strains and generated eight recombinant viruses by introducing single or multiple gene fragments from Margarita into the PdR backbone. All chimeric viruses had comparable replication characteristics in porcine monocyte-derived macrophages. Recombinant PdR viruses carrying either E2 or NS5A/NS5B of Margarita, with 36 or 5 uridines in the 3′UTR, remained low virulent in 3-month-old pigs. The combination of these elements recovered the high-virulent Margarita phenotype. These results show that CSFV evolution towards attenuated variants in the field involved mutations in both structural and non-structural proteins and the UTRs, which act synergistically to determine virulence. Full article
(This article belongs to the Special Issue Pestivirus 2024)
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13 pages, 2626 KiB  
Article
Multivariate Analysis as a Method to Evaluate Antigenic Relationships between Bovine Viral Diarrhea Virus 1b Isolates and Vaccine Strains
by Shollie M. Falkenberg, Hao Ma, Eduardo Casas, Rohana P. Dassanayake, Michael W. Bolton, Gage Raithel, Scott Silvis, John D. Neill and Paul H. Walz
Viruses 2023, 15(10), 2085; https://doi.org/10.3390/v15102085 - 13 Oct 2023
Viewed by 1157
Abstract
The antigenicity of bovine viral diarrhea virus (BVDV) has been evaluated using virus-neutralizing titer data analyzed by principal component analysis (PCA) and has demonstrated numerous isolates to be antigenically divergent from US vaccine strains. The lack of BVDV-1b strains in currently licensed vaccines [...] Read more.
The antigenicity of bovine viral diarrhea virus (BVDV) has been evaluated using virus-neutralizing titer data analyzed by principal component analysis (PCA) and has demonstrated numerous isolates to be antigenically divergent from US vaccine strains. The lack of BVDV-1b strains in currently licensed vaccines has raised concerns regarding the lack of protection against BVDV-1b field strains. The aim of this study was to evaluate the antigenic diversity of BVDV-1b strains and better understand the breadth of antigenic relatedness using BVDV-1b antisera and antisera from vaccine strains. Results from this analysis demonstrate the antigenic diversity observed among BVDV-1b isolates and genetic assignment into the BVDV-1b subgenotype is not representative of antigenic relatedness. This is demonstrated by BVDV-1b isolates (2280N, SNc, Illc, MSU, and 2337) observed to be as antigenically dissimilar as BVDV-2a isolates when using BVDV-1b antisera. Additionally, when BVDV-1a vaccine antisera was used for comparisons, a greater percentage of BVDV-1b isolates clustered with BVDV-1a vaccine strains as part of PC1, suggesting antigenic relatedness and potentially partial protection. Collectively, data from this study would suggest that while most BVDV-1b isolates are antigenically similar, there are antigenically dissimilar BVDV-1b isolates as determined by the lack of cross-reactivity, which may contribute to the lack of protection. Full article
(This article belongs to the Special Issue Pestivirus 2024)
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11 pages, 1491 KiB  
Article
Dynamics of Infection of Atypical Porcine Pestivirus in Commercial Pigs from Birth to Market: A Longitudinal Study
by Alexandra C. Buckley, Juan-Carlos Mora-Díaz, Ronaldo L. Magtoto, Amberly Van Hulzen, Franco Matias Ferreyra, Shollie M. Falkenberg, Luis G. Giménez-Lirola and Bailey L. Arruda
Viruses 2023, 15(8), 1767; https://doi.org/10.3390/v15081767 - 18 Aug 2023
Cited by 1 | Viewed by 1569
Abstract
Atypical porcine pestivirus (APPV) was found to be associated with pigs demonstrating congenital tremors (CT), and clinical signs in pigs have been reproduced after experimental challenge. Subsequently, APPV has been identified in both symptomatic and asymptomatic swine of all ages globally. The objective [...] Read more.
Atypical porcine pestivirus (APPV) was found to be associated with pigs demonstrating congenital tremors (CT), and clinical signs in pigs have been reproduced after experimental challenge. Subsequently, APPV has been identified in both symptomatic and asymptomatic swine of all ages globally. The objective of this research was to perform a longitudinal study following two cohorts of pigs, those born in litters with pigs exhibiting CT and those born in litters without CT, to analyze the virus and antibody dynamics of APPV infection in serum from birth to market. There was a wide range in the percentage of affected pigs (8–75%) within CT-positive litters. After co-mingling with CT-positive litters at weaning, pigs from CT-negative litters developed viremia that was cleared after approximately 2 months, with the majority seroconverting by the end of the study. In contrast, a greater percentage of pigs exhibiting CT remained PCR positive throughout the growing phase, with less than one-third of these animals seroconverting. APPV RNA was present in multiple tissues from pigs in both groups at the time of marketing. This study improved our understanding of the infection dynamics of APPV in swine and the impact that the immune status and timing of infection have on the persistence of APPV in serum and tissues. Full article
(This article belongs to the Special Issue Pestivirus 2024)
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13 pages, 4348 KiB  
Article
Structure of Bovine CD46 Ectodomain
by Hazel Aitkenhead, David I. Stuart and Kamel El Omari
Viruses 2023, 15(7), 1424; https://doi.org/10.3390/v15071424 - 23 Jun 2023
Cited by 1 | Viewed by 1585
Abstract
CD46, or membrane cofactor protein, is a type-one transmembrane protein from the complement regulatory protein family. Alongside its role in complement activation, CD46 is involved in many other processes, from T-cell activation to reproduction. It is also referred to as a pathogen magnet, [...] Read more.
CD46, or membrane cofactor protein, is a type-one transmembrane protein from the complement regulatory protein family. Alongside its role in complement activation, CD46 is involved in many other processes, from T-cell activation to reproduction. It is also referred to as a pathogen magnet, because it is used as a receptor by multiple bacteria and viruses. Bovine CD46 (bovCD46) in particular is involved in bovine viral diarrhoea virus entry, an economically important disease in cattle industries. This study presents the X-ray crystallographic structure of the extracellular region of bovCD46, revealing a four-short-consensus-repeat (SCR) structure similar to that in human CD46. SCR1-3 are arranged linearly, while SCR 4 has a reduced interface angle, resulting in a hockey stick-like appearance. The structure also reveals the bovine viral diarrhoea virus interaction site in SCR1, which is likely to confer pestivirus specificity for their target host, CD46. Insights gained from the structural information on pestivirus receptors, such as CD46, could offer valuable guidance for future control strategies. Full article
(This article belongs to the Special Issue Pestivirus 2024)
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