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14 pages, 3059 KiB

Open AccessArticle

Analysis of Swine Conventional Dendritic Cells, DEC205⁺CD172a^+/−CADM1⁺, from Blood and Spleen in Response to PRRSV and PEDV

by Héctor Parra-Sánchez, Lorena Bustamante-Córdova, Mónica Reséndiz, Verónica Mata-Haro, Araceli Pinelli-Saavedra and Jesús Hernández

Viruses 2019, 11(11), 1001; https://0-doi-org.brum.beds.ac.uk/10.3390/v11111001 - 31 Oct 2019

Cited by 10 | Viewed by 4120

Abstract

Conventional dendritic cells (cDCs) cannot be infected by porcine reproductive and respiratory syndrome virus (PRRSV) but respond to infection via cytokine production, indicating a possible role in initiation/regulation of the immune response against PRRSV. In this work, we evaluated the responses of splenic [...] Read more.

Conventional dendritic cells (cDCs) cannot be infected by porcine reproductive and respiratory syndrome virus (PRRSV) but respond to infection via cytokine production, indicating a possible role in initiation/regulation of the immune response against PRRSV. In this work, we evaluated the responses of splenic and blood cDCs, with DEC205⁺CADM1⁺CD172a^+/− phenotype, as well as those of CD163⁺ cells against PRRSV and porcine epidemic diarrhea virus (PEDV). Both populations were incubated in the presence of PRRSV or PEDV with and without naïve CD3⁺ T cells, and cytokine responses were evaluated by qPCR and ELISA. Our results showed that cDCs, but not CD163⁺ cells, produced IL-12 in response to PRRSV. PEDV did not induce IL-12 production. Cocultures of cDCs and autologous naïve CD3⁺ cells resulted in decreased IL-12 production and low expression of IFN-γ transcripts in response to PRRSV. Interestingly, cDCs increased the proliferation of naïve T cells in the presence of PRRSV compared with that achieved with monocytes and peripheral blood mononuclear cells (PBMCs). Cocultures of CD163⁺ cells induced IL-10 and IL-4 expression in the presence of PRRSV and PEDV, respectively. In conclusion, cDCs can selectively produce IL-12 in response to PRRSV but poorly participate in the activation of naïve T cells. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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18 pages, 3305 KiB

Open AccessArticle

PP2A Facilitates Porcine Reproductive and Respiratory Syndrome Virus Replication by Deactivating irf3 and Limiting Type I Interferon Production

by Jiayu Xu, Lu Zhang, Yunfei Xu, He Zhang, Junxin Gao, Qian Wang, Zhijun Tian, Lv Xuan, Hongyan Chen and Yue Wang

Viruses 2019, 11(10), 948; https://0-doi-org.brum.beds.ac.uk/10.3390/v11100948 - 15 Oct 2019

Cited by 6 | Viewed by 3262

Abstract

Protein phosphatase 2A (PP2A), a major serine/threonine phosphatase in mammalian cells, is known to regulate the kinase-driven intracellular signaling pathways. Emerging evidences have shown that the PP2A phosphatase functions as a bona-fide therapeutic target for anticancer therapy, but it is unclear whether PP2A [...] Read more.

Protein phosphatase 2A (PP2A), a major serine/threonine phosphatase in mammalian cells, is known to regulate the kinase-driven intracellular signaling pathways. Emerging evidences have shown that the PP2A phosphatase functions as a bona-fide therapeutic target for anticancer therapy, but it is unclear whether PP2A affects a porcine reproductive and respiratory syndrome virus infection. In the present study, we demonstrated for the first time that inhibition of PP2A activity by either inhibitor or small interfering RNA duplexes in target cells significantly reduced their susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) infection. Further analysis revealed that inhibition of PP2A function resulted in augmented production of type I interferon (IFN). The mechanism is that inhibition of PP2A activity enhances the levels of phosphorylated interferon regulatory factor 3, which activates the transcription of IFN-stimulated genes. Moreover, inhibition of PP2A activity mainly blocked PRRSV replication in the early stage of viral life cycle, after virus entry but before virus release. Using type I IFN receptor 2 specific siRNA in combination with PP2A inhibitor, we confirmed that the effect of PP2A on viral replication within target cells was an interferon-dependent manner. Taken together, these findings demonstrate that PP2A serves as a negative regulator of host cells antiviral responses and provides a novel therapeutic target for virus infection. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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22 pages, 5465 KiB

Open AccessArticle

Characterizing the PRRSV nsp2 Deubiquitinase Reveals Dispensability of Cis-Activity for Replication and a Link of nsp2 to Inflammation Induction

by Shaochuan Zhou, Xinna Ge, Can Kong, Teng Liu, Aijing Liu, Peng Gao, Jiangwei Song, Lei Zhou, Xin Guo, Jun Han and Hanchun Yang

Viruses 2019, 11(10), 896; https://0-doi-org.brum.beds.ac.uk/10.3390/v11100896 - 26 Sep 2019

Cited by 8 | Viewed by 3653

Abstract

The papain-like cysteine protease 2 (PLP2) within the N-terminus of the porcine reproductive and respiratory syndrome virus (PRRSV) nsp2 replicase protein specifies a deubiquitinating enzyme (DUB), but its biochemical properties and the role in infection have remained poorly defined. By using in vitro [...] Read more.

The papain-like cysteine protease 2 (PLP2) within the N-terminus of the porcine reproductive and respiratory syndrome virus (PRRSV) nsp2 replicase protein specifies a deubiquitinating enzyme (DUB), but its biochemical properties and the role in infection have remained poorly defined. By using in vitro assays, we found that the purified PLP2 could efficiently cleave K63 and K48 linked polyubiquitin chains Ub3-7 in vitro although displaying a differential activity in converting the respective ubiquitin dimers to monomer. The subsequent mutagenesis analyses revealed that the requirement for PLP2 DUB activity surprisingly resembled that for cis-cleavage activity, as several mutations (e.g., D91R, D85R, etc.) that largely ablated the DUB function also blocked the cis- but not trans-proteolytic cleavage of nsp2/3 polyprotein. Moreover, the analyses identified key mutations that could differentiate DUB from PLP2 cis- and trans-cleavage activities. Further reverse genetics analyses revealed the following findings: (i) mutations that largely blocked the DUB activity were all lethal to the virus, (ii) a point mutation T88G that selectively blocked the cis-cleavage activity of PLP2 did not affect viral viability in cell culture, and (iii) an E90Q mutation that did not affect either of the PLP2 activities led to rescue of WT-like virus but displayed significantly reduced ability to induce TNF-α production. Our findings support the possibility that the PLP2 DUB activity, but not cis-cleavage activity, is essential for PRRSV replication. The data also establish a strong link of nsp2 to pro-inflammatory cytokine induction during infection that operates in a manner independent of PLP2 DUB activity. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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13 pages, 1784 KiB

Open AccessArticle

Characterization of the Humoral Immune Response Induced after Infection with Atypical Porcine Pestivirus (APPV)

by Gökce Nur Cagatay, Denise Meyer, Michael Wendt, Paul Becher and Alexander Postel

Viruses 2019, 11(10), 880; https://0-doi-org.brum.beds.ac.uk/10.3390/v11100880 - 21 Sep 2019

Cited by 31 | Viewed by 3299

Abstract

Atypical porcine pestivirus (APPV) is a widely distributed pathogen causing congenital tremor (CT) in piglets. So far, no data are available regarding the humoral immune response against APPV. In this study, piglets and their sows from an affected herd were tested longitudinally for [...] Read more.

Atypical porcine pestivirus (APPV) is a widely distributed pathogen causing congenital tremor (CT) in piglets. So far, no data are available regarding the humoral immune response against APPV. In this study, piglets and their sows from an affected herd were tested longitudinally for viral genome and antibodies. APPV genome was detected in the majority of the piglets (14/15) from CT affected litters. Transient infection of gilts was observed. Kinetics of E^rns- and E2-specific antibodies and their neutralizing capacity were determined by recently (E^rns) and newly (E2) developed antibody ELISAs and virus neutralization assays. Putative maternally derived antibodies (MDA) were detected in most piglets, but displayed only low to moderate neutralizing capacity (ND₅₀ ≤ 112). Horizontal APPV transmission occurred when uninfected and infected piglets were mingled on the flat deck. Horizontally infected piglets were clinically inapparent and showed only transient viremia with subsequently consistently high E2 antibody levels. For piglets from CT affected litters, significantly lower neutralizing antibody titers were observed. Results indicate that E2 represents the main target of neutralizing antibodies. Characterization of the humoral immune response against APPV will help to provide valuable serological diagnosis, to understand the epidemiology of this novel pathogen, and to implement tailored prevention strategies. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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18 pages, 2491 KiB

Open AccessArticle

Serum-Derived Extracellular Vesicles from African Swine Fever Virus-Infected Pigs Selectively Recruit Viral and Porcine Proteins

by Sergio Montaner-Tarbes, Myriam Pujol, Tamara Jabbar, Philippa Hawes, Dave Chapman, Hernando del Portillo, Lorenzo Fraile, Pedro J. Sánchez-Cordón, Linda Dixon and Maria Montoya

Viruses 2019, 11(10), 882; https://0-doi-org.brum.beds.ac.uk/10.3390/v11100882 - 20 Sep 2019

Cited by 12 | Viewed by 4571

Abstract

: African swine fever is a devastating hemorrhagic infectious disease, which affects domestic and wild swines (Sus scrofa) of all breeds and ages, with a high lethality of up to 90–100% in naïve animals. The causative agent, African swine fever virus [...] Read more.

: African swine fever is a devastating hemorrhagic infectious disease, which affects domestic and wild swines (Sus scrofa) of all breeds and ages, with a high lethality of up to 90–100% in naïve animals. The causative agent, African swine fever virus (ASFV), is a large and complex double-stranded DNA arbovirus which is currently spreading worldwide, with serious socioeconomic consequences. There is no treatment or effective vaccine commercially available, and most of the current research is focused on attenuated viral models, with limited success so far. Thus, new strategies are under investigation. Extracellular vesicles (EVs) have proven to be a promising new vaccination platform for veterinary diseases in situations in which conventional approaches have not been completely successful. Here, serum extracellular vesicles from infected pigs using two different ASFV viruses (OURT 88/3 and Benin ΔMGF), corresponding to a naturally attenuated virus and a deletion mutant, respectively, were characterized in order to determine possible differences in the content of swine and viral proteins in EV-enriched fractions. Firstly, EVs were characterized by their CD5, CD63, CD81 and CD163 surface expression. Secondly, ASFV proteins were detected on the surface of EVs from ASFV-infected pig serum. Finally, proteomic analysis revealed few specific proteins from ASFV in the EVs, but 942 swine proteins were detected in all EV preparations (negative controls, and OURT 88/3 and Benin ΔMGF-infected preparations). However, in samples from OURT 88/3-infected animals, only a small number of proteins were differentially identified compared to control uninfected animals. Fifty-six swine proteins (Group Benin) and seven proteins (Group OURT 88/3) were differentially detected on EVs when compared to the EV control group. Most of these were related to coagulation cascades. The results presented here could contribute to a better understanding of ASFV pathogenesis and immune/protective responses in the host. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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16 pages, 3777 KiB

Open AccessArticle

No Evidence for a Role for Antibodies during Vaccination-Induced Enhancement of Porcine Reproductive and Respiratory Syndrome

by Carmen A. Sautter, Ivan Trus, Hans Nauwynck and Artur Summerfield

Viruses 2019, 11(9), 829; https://0-doi-org.brum.beds.ac.uk/10.3390/v11090829 - 06 Sep 2019

Cited by 5 | Viewed by 3216

Abstract

Vaccination is one of the most important tools to protect pigs against infection with porcine reproductive and respiratory syndrome virus 1 (PRRSV-1). Although neutralizing antibodies are considered to represent an important mechanism of protective immunity, anti-PRRSV antibodies, in particular at subneutralizing concentrations, have [...] Read more.

Vaccination is one of the most important tools to protect pigs against infection with porcine reproductive and respiratory syndrome virus 1 (PRRSV-1). Although neutralizing antibodies are considered to represent an important mechanism of protective immunity, anti-PRRSV antibodies, in particular at subneutralizing concentrations, have also been reported to exacerbate PRRSV infection, probably through FcγR-mediated uptake of antibody-opsonized PRRSV, resulting in enhanced infection of, and replication in, target cells. Therefore, we investigated this pathway using sera from an animal experiment in which vaccine-mediated enhancement of clinical symptoms was observed. Three groups of six pigs were vaccinated with an inactivated PRRSV vaccine based on the PRRSV-1 subtype 3 strain Lena and challenged after a single or a prime-boost immunization protocol, or injected with PBS. We specifically tested if sera obtained from these animals can enhance macrophage infections, viral shedding, or cytokine release at different dilutions. Neither the presence of neutralizing antibodies nor general anti-PRRSV antibodies, mediated an enhanced infection, increased viral release or cytokine production by macrophages. Taken together, our data indicate that the exacerbated disease was not caused by antibodies. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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27 pages, 1955 KiB

Open AccessArticle

The T-Cell Response to Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)

by Andrew R. Kick, Amanda F. Amaral, Lizette M. Cortes, Jonathan E. Fogle, Elisa Crisci, Glen W. Almond and Tobias Käser

Viruses 2019, 11(9), 796; https://0-doi-org.brum.beds.ac.uk/10.3390/v11090796 - 29 Aug 2019

Cited by 31 | Viewed by 5849

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause severe reproductive and respiratory pathologies resulting in immense monetary and welfare costs for the swine industry. The vaccines against PRRSV are available; but they struggle with providing protection against the plethora of heterologous [...] Read more.

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause severe reproductive and respiratory pathologies resulting in immense monetary and welfare costs for the swine industry. The vaccines against PRRSV are available; but they struggle with providing protection against the plethora of heterologous PRRSV strains. To improve PRRSV vaccine development, the aim of this study was to provide an in-depth analysis of the crucial heterologous T-cell response to type-2 PRRSV. Following PRRSV modified live virus (MLV) vaccination or infection using one high- or one low-pathogenic PRRSV-strain, this nine-week study evaluated the T-cell response to different PRRSV strains. Our results demonstrate an important role for T cells in this homo- and heterologous response. Specifically, the T-helper cells were the main responders during viremia. Their peak response at 28 dpi correlated with a reduction in viremia, and their homing receptor expression indicated the additional importance for the anti-PRRSV response in the lymphatic and lung tissue. The cytotoxic T lymphocyte (CTL) response was the strongest at the site of infection—the lung and bronchoalveolar lavage. The TCR-γδ T cells were the main responders post viremia and PRRSV induced their expression of the lymph node homing the chemokine receptor, CCR7: This indicates a crucial role for TCR-γδ T cells in the anti-PRRSV response in the lymphatic system. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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14 pages, 2614 KiB

Open AccessArticle

Basal Level p53 Suppresses Antiviral Immunity Against Foot-And-Mouth Disease Virus

by Tianliang Zhang, Haotai Chen, Xinsheng Liu, Linlin Qi, Xin Gao, Kailing Wang, Kaishen Yao, Jie Zhang, Yuefeng Sun, Yongguang Zhang and Run Wu

Viruses 2019, 11(8), 727; https://0-doi-org.brum.beds.ac.uk/10.3390/v11080727 - 07 Aug 2019

Cited by 2 | Viewed by 3490

Abstract

Tumor suppressor protein p53 (p53) is a master transcription factor that plays key roles in cell cycle arrest, apoptosis, senescence, and metabolism, as well as regulation of innate immunity during virus infection. In order to facilitate their replication and spreading, viruses have evolved [...] Read more.

Tumor suppressor protein p53 (p53) is a master transcription factor that plays key roles in cell cycle arrest, apoptosis, senescence, and metabolism, as well as regulation of innate immunity during virus infection. In order to facilitate their replication and spreading, viruses have evolved to manipulate p53 function through different strategies, with some requiring active p53 while others demand reduction/inhibition of p53 activity. However, there are no clear-cut reports about the roles of p53 during the infection of foot-and-mouth disease virus (FMDV), the causative agent of a highly contagious foot-and-mouth disease (FMD) of cloven-hoofed animals. Here we showed that p53 level was dynamically regulated during FMDV infection, being degraded at the early infection stage but recovered to the basal level at the late stage. Cells depleted of p53 showed inhibited FMDV replication and enhanced expression of the immune-related genes, whereas overexpression of p53 didn’t affect the viral replication. Viral challenge assay with p53 knockout mice obtained similar results, with viral load decreased, histopathological changes alleviated, and lifespan extended in the p53 knockout mice. Together, these data demonstrate that basal level p53 is required for efficient FMDV replication by suppressing the innate immunity. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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12 pages, 600 KiB

Open AccessArticle

Genetic Markers Associated with Field PRRSV-Induced Abortion Rates

by Ramona N. Pena, Carlos Fernández, María Blasco-Felip, Lorenzo J. Fraile and Joan Estany

Viruses 2019, 11(8), 706; https://0-doi-org.brum.beds.ac.uk/10.3390/v11080706 - 01 Aug 2019

Cited by 9 | Viewed by 3857

Abstract

In gilts and sows, the more severe clinical manifestation of porcine reproductive and respiratory syndrome virus (PRRSV) occurs in late gestation and can result in up to a 40% abortion incidence. Despite the known genetic component in resilience to PRRSV, there is scarce [...] Read more.

In gilts and sows, the more severe clinical manifestation of porcine reproductive and respiratory syndrome virus (PRRSV) occurs in late gestation and can result in up to a 40% abortion incidence. Despite the known genetic component in resilience to PRRSV, there is scarce information regarding the abortive outcome of this disease. We tested the relationship between eight molecular markers (six from published studies and two identified in the present study in the HDAC6 gene) and the probability of abortion during a PRRSV outbreak, using data from two commercial Landrace x Large White sow farms with an incidence of abortion of 35% and 17%. From the markers tested, USP18_-1533G>A did not segregate in these populations, and CD163_c.3534C>T and HDAC6_g.2360C>T did not affect the abortion rate. In contrast, the minor allele of two markers in SSC4 (WUR1000125 in GBP1 and rs340943904 in GBP5), which lower viremia in growing pigs, and the major alleles of CD163_rs1107556229 and HDAC6_rs325981825 were associated with a lower probability of abortion during PRRSV outbreaks. The more striking result was for the MX1 gene, where the odds ratio of aborting versus not aborting was nine times lower in the sows homozygous for a 275-bp insertion than in the other genotypes. Interactions between markers were not relevant. All together, we bring here the first evidence that mutations in the host genome can predispose or protect from complete reproductive failure in sows infected with PRRSV. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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14 pages, 2333 KiB

Open AccessArticle

Long-Term Circulation of Atypical Porcine Pestivirus (APPV) within Switzerland

by Cindy Kaufmann, Hanspeter Stalder, Xaver Sidler, Sandra Renzullo, Corinne Gurtner, Alexander Grahofer and Matthias Schweizer

Viruses 2019, 11(7), 653; https://0-doi-org.brum.beds.ac.uk/10.3390/v11070653 - 17 Jul 2019

Cited by 27 | Viewed by 3915

Abstract

In 2015, a new pestivirus was described in pig sera in the United States. This new “atypical porcine pestivirus” (APPV) was later associated with congenital tremor (CT) in newborn piglets. The virus appears to be distributed worldwide, but the limited knowledge of virus [...] Read more.

In 2015, a new pestivirus was described in pig sera in the United States. This new “atypical porcine pestivirus” (APPV) was later associated with congenital tremor (CT) in newborn piglets. The virus appears to be distributed worldwide, but the limited knowledge of virus diversity and the use of various diagnostic tests prevent direct comparisons. Therefore, we developed an APPV-specific real-time RT-PCR assay in the 5′UTR of the viral genome to investigate both retro- and prospectively the strains present in Switzerland and their prevalence in domestic pigs. Overall, 1080 sera obtained between 1986 and 2018 were analyzed, revealing a virus prevalence of approximately 13% in pigs for slaughter, whereas it was less than 1% in breeding pigs. In the prospective study, APPV was also detected in piglets displaying CT. None of the samples could detect the Linda virus, which is another new pestivirus recently reported in Austria. Sequencing and phylogenetic analysis revealed a broad diversity of APP viruses in Switzerland that are considerably distinct from sequences reported from other isolates in Europe and overseas. This study indicates that APPV has already been widely circulating in Switzerland for many years, mainly in young animals, with 1986 being the earliest report of APPV worldwide. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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13 pages, 1764 KiB

Open AccessArticle

Differential Effect of the Deletion of African Swine Fever Virus Virulence-Associated Genes in the Induction of Attenuation of the Highly Virulent Georgia Strain

by Elizabeth Ramirez-Medina, Elizabeth Vuono, Vivian O’Donnell, Lauren G. Holinka, Ediane Silva, Ayushi Rai, Sarah Pruitt, Consuelo Carrillo, Douglas P. Gladue and Manuel V. Borca

Viruses 2019, 11(7), 599; https://0-doi-org.brum.beds.ac.uk/10.3390/v11070599 - 02 Jul 2019

Cited by 40 | Viewed by 4898

Abstract

African swine fever virus (ASFV) is the etiological agent of an often lethal disease of domestic pigs, African swine fever (ASF). The ASFV Georgia 2007 isolate (ASFV-G) is responsible for the current epidemic situation in Europe and Asia. Genetically modified ASFVs containing deletions [...] Read more.

African swine fever virus (ASFV) is the etiological agent of an often lethal disease of domestic pigs, African swine fever (ASF). The ASFV Georgia 2007 isolate (ASFV-G) is responsible for the current epidemic situation in Europe and Asia. Genetically modified ASFVs containing deletions of virulence-associated genes have produced attenuated phenotypes and induced protective immunity in swine. Here we describe the differential behavior of two viral genes, NL (DP71L) and UK (DP96R), both originally described as being involved in virus virulence. Deletion of either of these genes efficiently attenuated ASFV strain E70. We demonstrated that deletion of the UK gene from the ASFV-G genome did not decrease virulence when compared to the parental virus. Conversely, deletion of the NL gene produced a heterogeneous response, with early death in one of the animals and transient fever in the other animals. With this knowledge, we attempted to increase the safety profile of the previously reported experimental vaccine ASFV-GΔ9GL/ΔUK by deleting the NL gene. A triple gene-deletion virus was produced, ASFV-GΔ9GL/ΔNL/ΔUK. Although ASFV-GΔ9GL/ΔNL/ΔUK replicated in primary cell cultures of swine macrophages, it demonstrated a severe replication deficiency in pigs, failing to induce protection against challenge with parental ASFV-G. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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19 pages, 17092 KiB

Open AccessArticle

A DNA Prime Immuno-Potentiates a Modified Live Vaccine against the Porcine Reproductive and Respiratory Syndrome Virus but Does Not Improve Heterologous Protection

by Cindy Bernelin-Cottet, Céline Urien, Maxence Fretaud, Christelle Langevin, Ivan Trus, Luc Jouneau, Fany Blanc, Jean-Jacques Leplat, Céline Barc, Olivier Boulesteix, Mickaël Riou, Marilyn Dysart, Sophie Mahé, Elisabeth Studsrub, Hans Nauwynck, Nicolas Bertho, Olivier Bourry and Isabelle Schwartz-Cornil

Viruses 2019, 11(6), 576; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060576 - 25 Jun 2019

Cited by 10 | Viewed by 5182

Abstract

The porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus inducing abortion in sows and respiratory disease in young pigs, is a leading infectious cause of economic losses in the swine industry. Modified live vaccines (MLVs) help in controlling the disease, but [...] Read more.

The porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus inducing abortion in sows and respiratory disease in young pigs, is a leading infectious cause of economic losses in the swine industry. Modified live vaccines (MLVs) help in controlling the disease, but their efficacy is often compromised by the high genetic diversity of circulating viruses, leading to vaccine escape variants in the field. In this study, we hypothesized that a DNA prime with naked plasmids encoding PRRSV antigens containing conserved T-cell epitopes may improve the protection of MLV against a heterologous challenge. Plasmids were delivered with surface electroporation or needle-free jet injection and European strain-derived PRRSV antigens were targeted or not to the dendritic cell receptor XCR1. Compared to MLV-alone, the DNA-MLV prime- boost regimen slightly improved the IFNγ T-cell response, and substantially increased the antibody response against envelope motives and the nucleoprotein N. The XCR1-targeting of N significantly improved the anti-N specific antibody response. Despite this immuno-potentiation, the DNA-MLV regimen did not further decrease the serum viral load or the nasal viral shedding of the challenge strain over MLV-alone. Finally, the heterologous protection, achieved in absence of detectable effective neutralizing antibodies, was not correlated to the measured antibody or to the IFNγ T-cell response. Therefore, immune correlates of protection remain to be identified and represent an important gap of knowledge in PRRSV vaccinology. This study importantly shows that a naked DNA prime immuno-potentiates an MLV, more on the B than on the IFNγ T-cell response side, and has to be further improved to reach cross-protection. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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19 pages, 1805 KiB

Open AccessArticle

A DNA-Modified Live Vaccine Prime–Boost Strategy Broadens the T-Cell Response and Enhances the Antibody Response against the Porcine Reproductive and Respiratory Syndrome Virus

by Cindy Bernelin-Cottet, Céline Urien, Elisabeth Stubsrud, Virginie Jakob, Edwige Bouguyon, Elise Bordet, Céline Barc, Olivier Boulesteix, Vanessa Contreras, Christophe Barnier-Quer, Nicolas Collin, Ivan Trus, Hans Nauwynck, Nicolas Bertho and Isabelle Schwartz-Cornil

Viruses 2019, 11(6), 551; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060551 - 14 Jun 2019

Cited by 9 | Viewed by 4115

Abstract

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) induces reproductive disorders in sows and respiratory illnesses in growing pigs and is considered as one of the main pathogenic agents responsible for economic losses in the porcine industry worldwide. Modified live PRRSV vaccines (MLVs) [...] Read more.

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) induces reproductive disorders in sows and respiratory illnesses in growing pigs and is considered as one of the main pathogenic agents responsible for economic losses in the porcine industry worldwide. Modified live PRRSV vaccines (MLVs) are very effective vaccine types against homologous strains but they present only partial protection against heterologous viral variants. With the goal to induce broad and cross-protective immunity, we generated DNA vaccines encoding B and T antigens derived from a European subtype 1 strain that include T-cell epitope sequences known to be conserved across strains. These antigens were expressed either in a native form or in the form of vaccibodies targeted to the endocytic receptor XCR1 and CD11c expressed by different types of antigen-presenting cells (APCs). When delivered in skin with cationic nanoparticles and surface electroporation, multiple DNA vaccinations as a stand-alone regimen induced substantial antibody and T-cell responses, which were not promoted by targeting antigens to APCs. Interestingly, a DNA-MLV prime–boost strategy strongly enhanced the antibody response and broadened the T-cell responses over the one induced by MLV or DNA-only. The anti-nucleoprotein antibody response induced by the DNA-MLV prime–boost was clearly promoted by targeting the antigen to CD11c and XCR1, indicating a benefit of APC-targeting on the B-cell response. In conclusion, a DNA-MLV prime–boost strategy, by enhancing the potency and breadth of MLV vaccines, stands as a promising vaccine strategy to improve the control of PRRSV in infected herds. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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16 pages, 3745 KiB

Open AccessArticle

Effects of Intranasal Pseudorabies Virus AH02LA Infection on Microbial Community and Immune Status in the Ileum and Colon of Piglets

by Chuanjian Zhang, Yamei Liu, Saisai Chen, Yongfeng Qiao, Yating Zheng, Mengwei Xu, Zhisheng Wang, Jibo Hou, Jichun Wang and Hongjie Fan

Viruses 2019, 11(6), 518; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060518 - 05 Jun 2019

Cited by 12 | Viewed by 3277

Abstract

Pseudorabies virus (PRV) variants broke out in china since 2011, causing high fever, respiratory distress, systemic neurological symptoms, and diarrhea in piglets. This study investigated the effect of intranasal PRV variant (AH02LA) infection on ileal and colonic bacterial communities and immune status in [...] Read more.

Pseudorabies virus (PRV) variants broke out in china since 2011, causing high fever, respiratory distress, systemic neurological symptoms, and diarrhea in piglets. This study investigated the effect of intranasal PRV variant (AH02LA) infection on ileal and colonic bacterial communities and immune status in piglets. Ten piglets (free of PRV) were assigned to PRV variant and control groups (uninfected). At day 5 after inoculation, all piglets were euthanized. No PRV was detected in the ileal and colonic mucosa. In the PRV group, we observed up-regulation of specific cytokines gene expression, down-regulation of intestinal barrier-related gene expression, and reduction of secretory immunoglobulin A (sIgA) concentration in the ileum and colon. PRV infection increased the diversity of ileal bacterial community composition. PRV infection reduced the abundance of some beneficial bacteria (Lactobacillus species in the ileum and colon; butyrate-producing bacteria species in the colon) and increased the abundance of potentially pathogenic Fusobacterium nucleatum in the ileum and Sphingomonas paucimobilis in the colon. Moreover, PRV infection decreased concentrations of the beneficial lactate in the ileum and butyrate in the colon. However, this study does not allow to evaluate whether the observed changes are directly due to the PRV infection or rather to indirect effects (fever, clinical signs and changes in diet), and will be our next research content. In summary, our findings provide evidence that intranasal PRV infection directly or indirectly brings gut health risks and implications, although no PRV was detected in the ileum and colon. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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13 pages, 1499 KiB

Open AccessArticle

Detection Patterns of Porcine Parvovirus (PPV) and Novel Porcine Parvoviruses 2 through 6 (PPV2–PPV6) in Polish Swine Farms

by Dagmara Miłek, Aleksandra Woźniak, Magdalena Guzowska and Tomasz Stadejek

Viruses 2019, 11(5), 474; https://0-doi-org.brum.beds.ac.uk/10.3390/v11050474 - 24 May 2019

Cited by 25 | Viewed by 5011

Abstract

Porcine parvovirus (PPV) is a major causative agent in reproductive failure, but in the last two decades many novel porcine parvoviruses were described and designated as porcine parvovirus 2 through 6 (PPV2–PPV6). However, their role for pig health is largely unknown. The aim [...] Read more.

Porcine parvovirus (PPV) is a major causative agent in reproductive failure, but in the last two decades many novel porcine parvoviruses were described and designated as porcine parvovirus 2 through 6 (PPV2–PPV6). However, their role for pig health is largely unknown. The aim of this study was to better understand the on-farm prevalence of PPVs in different age groups of pigs, and to assess the diagnostic applicability of testing different diagnostic materials. In total, 271 oral fluids, 1244 serum samples, and 1238 fecal samples were collected from 3–21-week-old pigs from 19 farms, and after pooling by 4–6, tested by real-time PCR. The results showed that PPVs are widely spread in Poland and that the highest detection rates were obtained for oral fluids (ranging from 10.7% (PPV1) to 48.7% (PPV2)). Fattening pigs were the age group with the most frequent detection of PPVs (ranging from 8.6% (PPV1) to 49.1% (PPV2)). Porcine parvoviruses were detected mostly in growing-finishing pigs and the infection persisted until the late fattening period, which may suggest the chronic character of the infection (especially for PPV2, which was found to commonly infect animals of all ages). Particularly low Ct values detected for PPV2, PPV3, PPV5, and PPV6 in serum pools from some farms suggested that these viruses may cause high levels of viremia in one or more individuals included in these pools. Further studies are needed to quantify the levels of PPVs viremia and to assess the impact in co-infections with other, often endemic pig viruses, such as porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV). Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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14 pages, 2961 KiB

Open AccessArticle

Characteristics of the Life Cycle of Porcine Deltacoronavirus (PDCoV) In Vitro: Replication Kinetics, Cellular Ultrastructure and Virion Morphology, and Evidence of Inducing Autophagy

by Pan Qin, En-Zhong Du, Wen-Ting Luo, Yong-Le Yang, Yu-Qi Zhang, Bin Wang and Yao-Wei Huang

Viruses 2019, 11(5), 455; https://0-doi-org.brum.beds.ac.uk/10.3390/v11050455 - 18 May 2019

Cited by 37 | Viewed by 5103

Abstract

Porcine deltacoronavirus (PDCoV) causes severe diarrhea and vomiting in affected piglets. The aim of this study was to establish the basic, in vitro characteristics of the life cycle such as replication kinetics, cellular ultrastructure, virion morphology, and induction of autophagy of PDCoV. Time-course [...] Read more.

Porcine deltacoronavirus (PDCoV) causes severe diarrhea and vomiting in affected piglets. The aim of this study was to establish the basic, in vitro characteristics of the life cycle such as replication kinetics, cellular ultrastructure, virion morphology, and induction of autophagy of PDCoV. Time-course analysis of viral subgenomic and genomic RNA loads and infectious titers indicated that one replication cycle of PDCoV takes 5 to 6 h. Electron microscopy showed that PDCoV infection induced the membrane rearrangements with double-membrane vesicles and large virion-containing vacuoles. The convoluted membranes structures described in alpha- and beta-coronavirus were not observed. PDCoV infection also increased the number of autophagosome-like vesicles in the cytoplasm of cells, and the autophagy response was detected by LC3 I/II and p62 Western blot analysis. For the first time, this study presents the picture of the PDCoV infection cycle, which is crucial to help elucidate the molecular mechanism of deltacoronavirus replication. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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18 pages, 4852 KiB

Open AccessArticle

Porcine Parvovirus Infection Causes Pig Placenta Tissue Damage Involving Nonstructural Protein 1 (NS1)-Induced Intrinsic ROS/Mitochondria-Mediated Apoptosis

by Jianlou Zhang, Jinghui Fan, Yan Li, Shuang Liang, Shanshan Huo, Xing Wang, Yuzhu Zuo, Dan Cui, Wenyan Li, Zhenyu Zhong and Fei Zhong

Viruses 2019, 11(4), 389; https://0-doi-org.brum.beds.ac.uk/10.3390/v11040389 - 25 Apr 2019

Cited by 25 | Viewed by 4879

Abstract

Porcine parvovirus (PPV) is an important pathogen causing reproductive failure in pigs. PPV-induced cell apoptosis has been recently identified as being involved in PPV-induced placental tissue damages resulting in reproductive failure. However, the molecular mechanism was not fully elucidated. Here we demonstrate that [...] Read more.

Porcine parvovirus (PPV) is an important pathogen causing reproductive failure in pigs. PPV-induced cell apoptosis has been recently identified as being involved in PPV-induced placental tissue damages resulting in reproductive failure. However, the molecular mechanism was not fully elucidated. Here we demonstrate that PPV nonstructural protein 1 (NS1) can induce host cell apoptosis and death, thereby indicating the NS1 may play a crucial role in PPV-induced placental tissue damages and reproductive failure. We have found that NS1-induced apoptosis was significantly inhibited by caspase 9 inhibitor, but not caspase 8 inhibitor, and transfection of NS1 gene into PK-15 cells significantly inhibited mitochondria-associated antiapoptotic molecules Bcl-2 and Mcl-1 expressions and enhanced proapoptotic molecules Bax, P21, and P53 expressions, suggesting that NS1-induced apoptosis is mainly through the mitochondria-mediated intrinsic apoptosis pathway. We also found that both PPV infection and NS1 vector transfection could cause host DNA damage resulting in cell cycle arrest at the G1 and G2 phases, trigger mitochondrial ROS accumulation resulting in mitochondria damage, and therefore, induce the host cell apoptosis. This study provides a molecular basis for elucidating PPV-induced cell apoptosis and reproductive failure. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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15 pages, 21174 KiB

Open AccessArticle

Porcine Epidemic Diarrhea Virus (PEDV) ORF3 Interactome Reveals Inhibition of Virus Replication by Cellular VPS36 Protein

by Challika Kaewborisuth, Yodying Yingchutrakul, Sittiruk Roytrakul and Anan Jongkaewwattana

Viruses 2019, 11(4), 382; https://0-doi-org.brum.beds.ac.uk/10.3390/v11040382 - 24 Apr 2019

Cited by 14 | Viewed by 5230

Abstract

The accessory protein ORF3 of porcine epidemic diarrhea virus (PEDV) has been proposed to play a key role in virus replication. However, our understanding of its function regarding virus and host interaction is still limited. In this study, we employed immunoprecipitation and mass [...] Read more.

The accessory protein ORF3 of porcine epidemic diarrhea virus (PEDV) has been proposed to play a key role in virus replication. However, our understanding of its function regarding virus and host interaction is still limited. In this study, we employed immunoprecipitation and mass spectrometry to screen for cellular interacting partners of ORF3. Gene ontology analysis of the host interactome highlighted the involvement of ORF3 in endosomal and immune signaling pathways. Among the identified ORF3-interacting proteins, the vacuolar protein-sorting-associated protein 36 (VPS36) was assessed for its role in PEDV replication. VPS36 was found to interact with ORF3 regardless of its GLUE domain. As a result of VPS36–ORF3 interaction, PEDV replication was substantially suppressed in cells overexpressing VPS36. Interestingly, the ORF3 protein expression was diminished in VPS36-overexpressing cells, an effect that could not be restored by treatment of lysosomal inhibitors. In addition, disruption of endogenously-expressed VPS36 by siRNA could partially augment PEDV replication. Taken together, our study provides mechanistic insights into the contribution of ORF3 in PEDV replication. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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16 pages, 2798 KiB

Open AccessArticle

The N-Terminal Domain of Spike Protein Is Not the Enteric Tropism Determinant for Transmissible Gastroenteritis Virus in Piglets

by Gang Wang, Rui Liang, Ziwei Liu, Zhou Shen, Jiale Shi, Yuejun Shi, Feng Deng, Shaobo Xiao, Zhen F. Fu and Guiqing Peng

Viruses 2019, 11(4), 313; https://0-doi-org.brum.beds.ac.uk/10.3390/v11040313 - 30 Mar 2019

Cited by 18 | Viewed by 5108

Abstract

Transmissible gastroenteritis virus (TGEV) is the etiologic agent of transmissible gastroenteritis in pigs, and the N-terminal domain of TGEV spike protein is generally recognized as both the virulence determinant and enteric tropism determinant. Here, we assembled a full-length infectious cDNA clone of TGEV [...] Read more.

Transmissible gastroenteritis virus (TGEV) is the etiologic agent of transmissible gastroenteritis in pigs, and the N-terminal domain of TGEV spike protein is generally recognized as both the virulence determinant and enteric tropism determinant. Here, we assembled a full-length infectious cDNA clone of TGEV in a bacterial artificial chromosome. Using a novel approach, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems efficiently and rapidly rescued another recombinant virus with a 224-amino-acid deletion in the N-terminal domain of the TGEV Spike gene (S_NTD224), which is analogous to the N-terminal domain of porcine respiratory coronavirus. S_NTD224 notably affected the TGEV growth kinetics in PK-15 cells but was not essential for recombinant virus survival. In animal experiments with 13 two-day-old piglets, the TGEV recombinant viruses with/without S_NTD224 deletion induced obvious clinical signs and mortality. Together, our results directly demonstrated that S_NTD224 of TGEV mildly influenced TGEV virulence but was not the enteric tropism determinant and provide new insights for the development of a new attenuated vaccine against TGEV. Importantly, the optimized reverse genetics platform used in this study will simplify the construction of mutant infectious clones and help accelerate progress in coronavirus research. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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13 pages, 2016 KiB

Open AccessArticle

Interaction of Structural Glycoprotein E2 of Classical Swine Fever Virus with Protein Phosphatase 1 Catalytic Subunit Beta (PPP1CB)

by Elizabeth A. Vuono, Elizabeth Ramirez-Medina, Lauren G. Holinka, Ryan Baker-Branstetter, Manuel V. Borca and Douglas P. Gladue

Viruses 2019, 11(4), 307; https://0-doi-org.brum.beds.ac.uk/10.3390/v11040307 - 29 Mar 2019

Cited by 12 | Viewed by 3609

Abstract

Classical swine fever virus (CSFV) E2 protein, the major virus structural glycoprotein, is an essential component of the viral envelope. E2 is involved in virus absorption, induction of a protective immune response and is critical for virulence in swine. Using the yeast two-hybrid [...] Read more.

Classical swine fever virus (CSFV) E2 protein, the major virus structural glycoprotein, is an essential component of the viral envelope. E2 is involved in virus absorption, induction of a protective immune response and is critical for virulence in swine. Using the yeast two-hybrid system, we identified protein phosphatase 1 catalytic subunit beta (PPP1CB), which is part of the Protein Phosphatase 1 (PP1) complex, as a specific binding host partner for E2. We further confirmed the occurrence of this interaction in CSFV-infected swine cells by using two independent methodologies: Co-immunoprecipitation and Proximity Ligation Assay. In addition, we demonstrated that pharmacological activation of the PP1 pathway has a negative effect on CSFV replication while inhibition of the PP1 pathway or knockdown of PPP1CB by siRNA had no observed effect. Overall, our data suggests that the CSFV E2 and PPP1CB protein interact in infected cells, and that activation of the PP1 pathway decreases virus replication. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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13 pages, 2412 KiB

Open AccessArticle

A Field Recombinant Strain Derived from Two Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-1) Modified Live Vaccines Shows Increased Viremia and Transmission in SPF Pigs

by Julie Eclercy, Patricia Renson, Arnaud Lebret, Edouard Hirchaud, Valérie Normand, Mathieu Andraud, Frédéric Paboeuf, Yannick Blanchard, Nicolas Rose and Olivier Bourry

Viruses 2019, 11(3), 296; https://0-doi-org.brum.beds.ac.uk/10.3390/v11030296 - 23 Mar 2019

Cited by 48 | Viewed by 4909

Abstract

In Europe, modified live vaccines (MLV) are commonly used to control porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, they have been associated with safety issues such as reversion to virulence induced by mutation and/or recombination. On a French pig farm, we [...] Read more.

In Europe, modified live vaccines (MLV) are commonly used to control porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, they have been associated with safety issues such as reversion to virulence induced by mutation and/or recombination. On a French pig farm, we identified a field recombinant strain derived from two PRRSV-1 MLV (MLV1). As a result, we aimed to evaluate its clinical, virological, and transmission parameters in comparison with both parental strains. Three groups with six pigs in each were inoculated with either one of the two MLV1s or with the recombinant strain; six contact pigs were then added into each inoculated group. The animals were monitored daily for 35 days post-inoculation (dpi) for clinical symptoms; blood samples and nasal swabs were collected twice a week. PRRS viral load in inoculated pigs of recombinant group was higher in serum, nasal swabs, and tonsils in comparison with both vaccine groups. The first viremic contact pig was detected as soon as 2 dpi in the recombinant group compared to 10 and 17 dpi for vaccine groups. Estimation of transmission parameters revealed fastest transmission and longest duration of infectiousness for recombinant group. Our in vivo study showed that the field recombinant strain derived from two MLV1s demonstrated high viremia, shedding and transmission capacities. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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15 pages, 10360 KiB

Open AccessArticle

A Single V672F Substitution in the Spike Protein of Field-Isolated PEDV Promotes Cell–Cell Fusion and Replication in VeroE6 Cells

by Asawin Wanitchang, Janya Saenboonrueng, Challika Kaewborisuth, Kanjana Srisutthisamphan and Anan Jongkaewwattana

Viruses 2019, 11(3), 282; https://0-doi-org.brum.beds.ac.uk/10.3390/v11030282 - 20 Mar 2019

Cited by 8 | Viewed by 5217

Abstract

While porcine epidemic diarrhea virus (PEDV) infects and replicates in enterocytes lining villi of neonatal piglets with high efficiency, naturally isolated variants typically grow poorly in established cell lines, unless adapted by multiple passages. Cells infected with most cell-adapted PEDVs usually displayed large [...] Read more.

While porcine epidemic diarrhea virus (PEDV) infects and replicates in enterocytes lining villi of neonatal piglets with high efficiency, naturally isolated variants typically grow poorly in established cell lines, unless adapted by multiple passages. Cells infected with most cell-adapted PEDVs usually displayed large syncytia, a process triggered by the spike protein (S). To identify amino acids responsible for S-mediated syncytium formation, we constructed and characterized chimeric S proteins of the cell-adapted variant, YN144, in which the receptor binding domain (RBD) and S1/S2 cleavage site were replaced with those of a poorly culturable field isolate (G2). We demonstrated that the RBD, not the S1/S2 cleavage site, is critical for syncytium formation mediated by chimeric S proteins. Further mutational analyses revealed that a single mutation at the amino acid residue position 672 (V672F) could enable the chimeric S with the entire RBD derived from the G2 strain to trigger large syncytia. Moreover, recombinant PEDV viruses bearing S of the G2 strain with the single V672F substitution could induce extensive syncytium formation and replicate efficiently in VeroE6 cells stably expressing porcine aminopeptidase N (VeroE6-APN). Interestingly, we also demonstrated that while the V672F mutation is critical for the syncytium formation in VeroE6-APN cells, it exerts a minimal effect in Huh-7 cells, thereby suggesting the difference in receptor preference of PEDV among host cells. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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11 pages, 1226 KiB

Open AccessArticle

Retrospective Detection and Genetic Characterization of Porcine circovirus 3 (PCV3) Strains Identified between 2006 and 2007 in Brazil

by Giuliana Loreto Saraiva, Pedro Marcus Pereira Vidigal, Viviane Sisdelli Assao, Murilo Leone Miranda Fajardo, Alerrandra Nunes Saraiva Loreto, Juliana Lopes Rangel Fietto, Gustavo Costa Bressan, Zélia Inês Portela Lobato, Márcia Rogéria de Almeida and Abelardo Silva-Júnior

Viruses 2019, 11(3), 201; https://0-doi-org.brum.beds.ac.uk/10.3390/v11030201 - 27 Feb 2019

Cited by 34 | Viewed by 4157

Abstract

Porcine circovirus 3 (PCV3) is an emerging virus that was first identified in the United States in 2016. Since its first detection, PCV3 has already been found in America, Asia, and Europe. Although PCV3 has already been described in Brazil, knowledge of its [...] Read more.

Porcine circovirus 3 (PCV3) is an emerging virus that was first identified in the United States in 2016. Since its first detection, PCV3 has already been found in America, Asia, and Europe. Although PCV3 has already been described in Brazil, knowledge of its detection and sequence variation before 2016 is limited, as well as its distribution in the main swine producing regions of Brazil. In this study, 67 porcine clinical samples collected from nine states in Brazil between 2006 and 2007 were analyzed for PCV3 infection by PCR. Results showed that 47.8% of the samples were PCV3 positive, across all nine states. Of the PCV3-positive samples, 37.5% were also positive for PCV2. Interestingly, no clinical signs were associated with samples that were detected singularly with PCV3 infection. Moreover, the positive PCV3 rate in healthy pigs was higher (29.8%) than that found in unhealthy pigs (17.9%), suggesting that most pigs could live with PCV3 infection without any clinical sign in the analyzed samples. Nucleotide sequence analysis showed that PCV3 strains obtained in this study shared 94.44% to 99.83% sequence identity at the open reading frame 2 (ORF2) gene level with available strains from different countries. PCV3 Brazilian sequences collected in 2006 and 2007 shared 97.94% to 99.62% identity with the strains obtained in 2016. The results of neutrality and selective pressure tests indicated that the PCV3 Cap protein seems unable to tolerate high levels of variation on its sequence. Phylogenetic analysis grouped the Brazilian strains in PCV3a and PCV3b genotypes clusters, both including strains collected in America, Asia, and Europe. Taking the results together, multiple events of introduction of PCV3 may have occurred in Brazil, and Brazilian PCV3 strains may show genetic stability over the past 10 years. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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Review

Jump to: Research

27 pages, 923 KiB

Open AccessReview

How Central Is the Domestic Pig in the Epidemiological Cycle of Japanese Encephalitis Virus? A Review of Scientific Evidence and Implications for Disease Control

by Héléna Ladreyt, Benoit Durand, Philippe Dussart and Véronique Chevalier

Viruses 2019, 11(10), 949; https://0-doi-org.brum.beds.ac.uk/10.3390/v11100949 - 15 Oct 2019

Cited by 37 | Viewed by 5885

Abstract

Despite the existence of human vaccines, Japanese encephalitis (JE) remains the leading cause of human encephalitis in Asia. Pigs are described as the main amplifying host, but their role in JE epidemiology needs to be reassessed in order to identify and implement efficient [...] Read more.

Despite the existence of human vaccines, Japanese encephalitis (JE) remains the leading cause of human encephalitis in Asia. Pigs are described as the main amplifying host, but their role in JE epidemiology needs to be reassessed in order to identify and implement efficient control strategies, for both human and animal health. We aimed to provide a systematic review of publications linked to JE in swine, in terms of both individual and population characteristics of JE virus (JEV) infection and circulation, as well as observed epidemiological patterns. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to select and analyze relevant articles from the Scopus database, 127 of which were included in the review. Pigs are central, but the implication of secondary hosts cannot be ruled out and should be further investigated. Although human vaccination cannot eradicate the virus, it is clearly the most important means of preventing human disease. However, a better understanding of the actual involvement of domestic pigs as well as other potential JEV hosts in different JEV epidemiological cycles and patterns could help to identify additional/complementary control measures, either by targeting pigs or not, and in some specific epidemiological contexts, contribute to reduce virus circulation and protect humans from JEV infection. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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14 pages, 1930 KiB

Open AccessReview

An Update on African Swine Fever Virology

by Axel Karger, Daniel Pérez-Núñez, Jesús Urquiza, Patricia Hinojar, Covadonga Alonso, Ferdinando B. Freitas, Yolanda Revilla, Marie-Frédérique Le Potier and Maria Montoya

Viruses 2019, 11(9), 864; https://0-doi-org.brum.beds.ac.uk/10.3390/v11090864 - 17 Sep 2019

Cited by 86 | Viewed by 10453

Abstract

Animal diseases constitute a continuing threat to animal health, food safety, national economy, and the environment. Among those, African swine fever (ASF) is one of the most devastating viruses affecting pigs and wild suids due to the lack of vaccine or effective treatment. [...] Read more.

Animal diseases constitute a continuing threat to animal health, food safety, national economy, and the environment. Among those, African swine fever (ASF) is one of the most devastating viruses affecting pigs and wild suids due to the lack of vaccine or effective treatment. ASF is endemic in countries in sub-Saharan Africa, but since its introduction to the Caucasus region in 2007, a highly virulent strain of ASF virus (ASFV) has continued to circulate and spread into Eastern Europe and Russia, and most recently into Western Europe, China, and various countries of Southeast Asia. Given the importance of this disease, this review will highlight recent discoveries in basic virology with special focus on proteomic analysis, replication cycle, and some recent data on genes involved in cycle progression and viral–host interactions, such as I215L (E2 ubiquitin-conjugating enzyme), EP402R (CD2v), A104R (histone-like protein), QP509L, and Q706L (RNA helicases) or P1192R (Topoisomerase II). Taking into consideration the large DNA genome of ASFV and its complex interactions with the host, more studies and new approaches are to be taken to understand the basic virus–host interaction for ASFV. Proteomic studies are just paving the way for future research. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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13 pages, 286 KiB

Open AccessReview

African Swine Fever: Disease Dynamics in Wild Boar Experimentally Infected with ASFV Isolates Belonging to Genotype I and II

by Pedro J. Sánchez-Cordón, Alejandro Nunez, Aleksija Neimanis, Emil Wikström-Lassa, María Montoya, Helen Crooke and Dolores Gavier-Widén

Viruses 2019, 11(9), 852; https://0-doi-org.brum.beds.ac.uk/10.3390/v11090852 - 13 Sep 2019

Cited by 44 | Viewed by 6580

Abstract

After the re-introduction of African swine fever virus (ASFV) genotype II isolates into Georgia in 2007, the disease spread from Eastern to Western Europe and then jumped first up to Mongolian borders and later into China in August 2018, spreading out of control [...] Read more.

After the re-introduction of African swine fever virus (ASFV) genotype II isolates into Georgia in 2007, the disease spread from Eastern to Western Europe and then jumped first up to Mongolian borders and later into China in August 2018, spreading out of control and reaching different countries of Southeast Asia in 2019. From the initial incursion, along with domestic pigs, wild boar displayed a high susceptibility to ASFV and disease development. The disease established self-sustaining cycles within the wild boar population, a key fact that helped its spread and that pointed to the wild boar population as a substantial reservoir in Europe and probably also in Asia, which may hinder eradication and serve as the source for further geographic expansion. The present review gathers the most relevant information available regarding infection dynamics, disease pathogenesis and immune response that experimental infections with different ASFV isolates belonging to genotype I and II in wild boar and feral pigs have generated. Knowledge gaps in areas such as disease pathogenesis and immune response highlights the importance of focusing future studies on unravelling the early mechanisms of virus-cell interaction and innate and/or adaptive immune responses, knowledge that will contribute to the development of efficacious treatments/vaccines against ASFV. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

17 pages, 266 KiB

Open AccessReview

Aerosol Detection and Transmission of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): What Is the Evidence, and What Are the Knowledge Gaps?

by Andréia Gonçalves Arruda, Steve Tousignant, Juan Sanhueza, Carles Vilalta, Zvonimir Poljak, Montserrat Torremorell, Carmen Alonso and Cesar A Corzo

Viruses 2019, 11(8), 712; https://0-doi-org.brum.beds.ac.uk/10.3390/v11080712 - 03 Aug 2019

Cited by 36 | Viewed by 6846

Abstract

In human and veterinary medicine, there have been multiple reports of pathogens being airborne under experimental and field conditions, highlighting the importance of this transmission route. These studies shed light on different aspects related to airborne transmission such as the capability of pathogens [...] Read more.

In human and veterinary medicine, there have been multiple reports of pathogens being airborne under experimental and field conditions, highlighting the importance of this transmission route. These studies shed light on different aspects related to airborne transmission such as the capability of pathogens becoming airborne, the ability of pathogens to remain infectious while airborne, the role played by environmental conditions in pathogen dissemination, and pathogen strain as an interfering factor in airborne transmission. Data showing that airborne pathogens originating from an infectious individual or population can infect susceptible hosts are scarce, especially under field conditions. Furthermore, even though disease outbreak investigations have generated important information identifying potential ports of entry of pathogens into populations, these investigations do not necessarily yield clear answers on mechanisms by which pathogens have been introduced into populations. In swine, the aerosol transmission route gained popularity during the late 1990’s as suspicions of airborne transmission of porcine reproductive and respiratory syndrome virus (PRRSV) were growing. Several studies were conducted within the last 15 years contributing to the understanding of this transmission route; however, questions still remain. This paper reviews the current knowledge and identifies knowledge gaps related to PRRSV airborne transmission. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

14 pages, 1486 KiB

Open AccessReview

Porcine Interferon Complex and Co-Evolution with Increasing Viral Pressure after Domestication

by Jordan Jennings and Yongming Sang

Viruses 2019, 11(6), 555; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060555 - 15 Jun 2019

Cited by 16 | Viewed by 4301

Abstract

Consisting of nearly 60 functional genes, porcine interferon (IFN)-complex represents an evolutionary surge of IFN evolution in domestic ungulate species. To compare with humans and mice, each of these species contains about 20 IFN functional genes, which are better characterized using the conventional [...] Read more.

Consisting of nearly 60 functional genes, porcine interferon (IFN)-complex represents an evolutionary surge of IFN evolution in domestic ungulate species. To compare with humans and mice, each of these species contains about 20 IFN functional genes, which are better characterized using the conventional IFN-α/β subtypes as examples. Porcine IFN-complex thus represents an optimal model for studying IFN evolution that resulted from increasing viral pressure during domestication and industrialization. We hypothesize and justify that porcine IFN-complex may extend its functionality in antiviral and immunomodulatory activity due to its superior molecular diversity. Furthermore, these unconventional IFNs could even confer some functional and signaling novelty beyond that of the well-studied IFN-α/β subtypes. Investigations into porcine IFN-complex will further our understanding of IFN biology and promote IFN-based therapeutic designs to confront swine viral diseases. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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17 pages, 2590 KiB

Open AccessReview

Porcine Dendritic Cells and Viruses: An Update

by Giulia Franzoni, Simon P. Graham, Silvia Dei Giudici and Annalisa Oggiano

Viruses 2019, 11(5), 445; https://0-doi-org.brum.beds.ac.uk/10.3390/v11050445 - 16 May 2019

Cited by 18 | Viewed by 5863

Abstract

Several viral infections of swine are responsible for major economic losses and represent a threat to the swine industry worldwide. New tools are needed to prevent and control endemic, emerging, and re-emerging viral diseases. Dendritic cells (DC) play a central role in linking [...] Read more.

Several viral infections of swine are responsible for major economic losses and represent a threat to the swine industry worldwide. New tools are needed to prevent and control endemic, emerging, and re-emerging viral diseases. Dendritic cells (DC) play a central role in linking the innate and adaptive arms of the immune system, so knowledge regarding their interaction with pathogens is necessary to understand the mechanisms underlying diseases pathogenesis and protection. In the first part of this review, we provide an update on the heterogeneous cell subsets that comprise the porcine DC family. In the second part of this review, we provide an overview of how three viruses, affecting pork production at a global level, African swine fever virus (ASFV), classical swine fever virus (CSFV), and porcine circovirus 2 (PCV2), modulate DC function. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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14 pages, 243 KiB

Open AccessReview

Co-Infection of Swine with Porcine Circovirus Type 2 and Other Swine Viruses

by Ting Ouyang, Xinwei Zhang, Xiaohua Liu and Linzhu Ren

Viruses 2019, 11(2), 185; https://0-doi-org.brum.beds.ac.uk/10.3390/v11020185 - 21 Feb 2019

Cited by 114 | Viewed by 8539

Abstract

Porcine circovirus 2 (PCV2) is the etiological agent that causes porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD), which are present in every major swine-producing country in the world. PCV2 infections may downregulate the host immune system and enhance the infection and replication [...] Read more.

Porcine circovirus 2 (PCV2) is the etiological agent that causes porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD), which are present in every major swine-producing country in the world. PCV2 infections may downregulate the host immune system and enhance the infection and replication of other pathogens. However, the exact mechanisms of PCVD/PCVAD are currently unknown. To date, many studies have reported that several cofactors, such as other swine viruses or bacteria, vaccination failure, and stress or crowding, in combination with PCV2, lead to PCVD/PCVAD. Among these cofactors, co-infection of PCV2 with other viruses, such as porcine reproductive and respiratory syndrome virus, porcine parvovirus, swine influenza virus and classical swine fever virus have been widely studied for decades. In this review, we focus on the current state of knowledge regarding swine co-infection with different PCV2 genotypes or strains, as well as with PCV2 and other swine viruses. Full article

(This article belongs to the Special Issue Porcine Viruses 2019)

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