18 results on '"Murtaugh Michael P"'
Search Results
2. Characterization of age-related susceptibility of macrophages to porcine reproductive and respiratory syndrome virus.
- Author
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Gray DK, Dvorak CMT, Robinson SR, and Murtaugh MP
- Subjects
- Age Factors, Animals, Cells, Cultured, Immunity, Innate, Swine, Macrophages virology, Porcine respiratory and reproductive syndrome virus growth & development, Porcine respiratory and reproductive syndrome virus immunology
- Abstract
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the most economically important disease affecting swine production worldwide. The severity and susceptibility of PRRSV infection varies with age. Nursery pigs have been shown to be more susceptible to PRRSV infection and a more severe and prolonged infection is observed as compared to growing or adult pigs. However, antibody responses to PRRSV are observed independent of age. Swine are the only known hosts of PRRSV, infection is restricted to cells of monocytic lineage, and fully differentiated porcine alveolar macrophages are the primary target of natural infection. Pulmonary intravascular macrophages from young pigs have been shown to be more susceptible to infection than those from adult pigs. A better understanding of why young pigs and macrophages from young pigs are more susceptible to PRRSV infection is critical to identify mechanisms of infection that can be explored for enhanced treatment or prevention of disease. This study examined PRRSV susceptibility of porcine alveolar macrophages isolated from the lungs of pigs of different age groups, and the presence of cell surface receptors to determine if differences correlated with infection level. The younger the pigs were, the more susceptible the macrophage were to PRRSV infection, but no differences in cellular receptor expression were observed between pigs of different ages. Resistance to infection is likely related to intracellular innate immune mechanisms rather than receptor-mediated entry., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
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3. Porcine circovirus 2 infection induces IFNβ expression through increased expression of genes involved in RIG-I and IRF7 signaling pathways.
- Author
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Dvorak CMT, Puvanendiran S, and Murtaugh MP
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- Animals, Circoviridae Infections genetics, Circoviridae Infections virology, Circovirus genetics, DEAD Box Protein 58 genetics, Interferon Regulatory Factor-7 genetics, Interferon-beta genetics, Signal Transduction, Swine, Swine Diseases genetics, Swine Diseases virology, Circoviridae Infections metabolism, Circovirus physiology, DEAD Box Protein 58 metabolism, Interferon Regulatory Factor-7 metabolism, Interferon-beta metabolism, Swine Diseases metabolism
- Abstract
Porcine circovirus-associated disease (PCVAD), caused by porcine circovirus 2 (PCV2), is characterized by a highly variable pathogenesis that is manifested by various disease syndromes and includes immune evasion. Hence, even though PCVAD is effectively controlled by vaccination, pigs and farms remain infected so that continued vaccination is necessary to control disease. We investigated the molecular interactions of PCV2 and its permissive VR1BL host cell for gene expression signatures that could provide insight into mechanisms leading towards disease. Molecular pathways involved in the innate immune response to PCV2 infection were examined to identify changes in gene expression associated with productive infection of VR1BL cells. RNA profiling from infected and uninfected cells showed that 139 genes were induced by infection and 43 genes were down-regulated, using a p value <0.05 and an absolute fold-change difference>2. A strong type 1 interferon response, including an increase in genes involved in the RIG-I/MDA5 pathway and downstream interferon induced genes, was observed. Key regulators involved in PCV2 infection were identified as IFNβ, DDX58 (RIG-I), and IRF7. PCV2 infection induces a strong interferon response which unexpectedly facilitates viral gene expression, perhaps due to the presence of an interferon-sensitive response element in the viral promoter. The findings suggest that PCV2 interventions that attenuate type 1 interferon responses at the cellular level might enhance immunity and eliminate persistent infection., (Published by Elsevier B.V.)
- Published
- 2018
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4. Porcine reproductive and respiratory syndrome virus neutralizing antibodies provide in vivo cross-protection to PRRSV1 and PRRSV2 viral challenge.
- Author
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Robinson SR, Rahe MC, Gray DK, Martins KV, and Murtaugh MP
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- Animals, Genotype, Immunity, Humoral, Immunization, Passive, Immunoglobulin G immunology, Porcine Reproductive and Respiratory Syndrome prevention & control, Porcine respiratory and reproductive syndrome virus classification, Porcine respiratory and reproductive syndrome virus genetics, Swine, Viral Proteins immunology, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Cross Protection immunology, Porcine Reproductive and Respiratory Syndrome immunology, Porcine Reproductive and Respiratory Syndrome virology, Porcine respiratory and reproductive syndrome virus immunology
- Abstract
Vaccine control and prevention of porcine reproductive and respiratory syndrome (PRRS), the most important disease of swine, is difficult to achieve. However, the discovery of broadly neutralizing antibody activity against porcine reproductive and respiratory syndrome virus (PRRSV) under typical field conditions opens the door to new immunologic approaches for robust protection. We show here that passive administration of purified immunoglobulins with neutralizing antibodies reduced PRRSV2 infection by up to 96%, and PRRSV1 infection by up to 87%, whereas immune immunoglobulins lacking neutralizing activity had no effect on viral infection. Hence, immune competence of passive immunoglobulin transfer was associated specifically with antibody neutralizing activity. Current models of PRRSV infection implicate a minor envelope glycoprotein (GP) complex including GP2, GP3, and GP4, as critical to permissive cell infection. However, conserved peptides comprising the putative cell attachment structure did not attenuate neutralization or viral infection. The results show that immunological approaches aimed at induction of broadly neutralizing antibodies may substantially enhance immune protection against PRRSV. The findings further show that naturally occurring viral isolates are able to induce protective humoral immunity against unrelated PRRSV challenge, thus removing a major conceptual barrier to vaccine development., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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5. Characterization of anti-porcine epidemic diarrhea virus neutralizing activity in mammary secretions.
- Author
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Song Q, Stone S, Drebes D, Greiner LL, Dvorak CMT, and Murtaugh MP
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- Animals, Antibodies, Neutralizing blood, Antibodies, Viral blood, Antigens, Viral immunology, Chlorocebus aethiops, Enzyme-Linked Immunosorbent Assay, Female, Immunoglobulin A blood, Immunoglobulin A immunology, Immunoglobulin G blood, Immunoglobulin G immunology, Lactation, Milk immunology, Neutralization Tests, Spike Glycoprotein, Coronavirus immunology, Swine, Swine Diseases diagnosis, Vero Cells, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Coronavirus Infections veterinary, Porcine epidemic diarrhea virus immunology, Swine Diseases immunology, Swine Diseases virology
- Abstract
Porcine epidemic diarrhea virus (PEDV) causes a severe clinical enteric disease in suckling neonates with up to 100% mortality, resulting in devastating economic losses to the pork industry in recent years. Maternal immunity via colostrum and milk is a vital source to neonates of passive protection against diarrhea, dehydration and death caused by PEDV. Comprehensive information on neutralizing activity (NA) against PEDV in mammary secretions is critically important for assessing the protective capacity of sows. Therefore, the objectives of this study were to characterize anti-PEDV neutralizing activity in mammary secretions. Anti-PEDV NA was present in colostrum, milk and serum from PEDV-infected sows as determined both by immunofluorescence and ELISA-based neutralizing assays, with neutralization levels higher in colostrum and milk than in serum. The highest NA was observed in colostrum on day 1, and decreased rapidly in milk at day 3, then gradually declined from day 3 to day 19 post-farrowing. Notably, the NA in mammary secretions showed various patterns of decline over time of lactation that may contribute to variation in sow protective capacities. The kinetics of NA decline were associated with total IgA and IgG antibody levels. Neutralizing activity significantly correlated with specific IgA primarily to spike domain 1 (S1) and domain 2 (S2) proteins of PEDV rather than to specific IgG in colostrum. Subsequently, the NA in milk was mainly related to specific IgA to S1 and S2 during lactation., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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6. Diagnostic phylogenetics reveals a new Porcine circovirus 2 cluster.
- Author
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Davies B, Wang X, Dvorak CM, Marthaler D, and Murtaugh MP
- Subjects
- Animals, Biodiversity, Circovirus genetics, DNA, Viral, Genetic Variation, Open Reading Frames, Phylogeny, Sequence Analysis, DNA, Circovirus classification
- Abstract
Porcine circovirus 2 (PCV2) was prevalent in swine in the United States before PCV2-associated disease (PCVAD) appeared in 2006. Limited nucleotide sequencing of open reading frame 2 (ORF2) encoding capsid, the only structural protein, revealed the presence of two genotypes, PCV2a and PCV2b. Later, PCV2c and mutant PCV2b, or PCV2d, were also described. However, extensive PCV2 ORF2 sequence databases in veterinary diagnostic laboratories have not been analyzed systematically to determine the genetic diversity of field isolates. Here, we interrogated >1100 PCV2 ORF2 nucleotide sequences to assess population diversity and genetic variation. We detected a novel PCV2 genotype that is substantially different, primarily in ORF2, from all known PCV2. Notably, ORF2 contains a unique carboxyl terminal amino acid insertion resulting in a 238 amino acid ORF2. All other PCV2 ORF2 proteins are 233 or 234 aa in length. Phylogenetic analysis indicates that it is more ancient than other PCV2 genotypes. The findings demonstrate the value of analyzing routine diagnostic laboratory sequence databases in population genetic analyses of animal pathogens., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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7. Emergence of a virulent porcine reproductive and respiratory syndrome virus in vaccinated herds in the United States.
- Author
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Wang X, Marthaler D, Rovira A, Rossow S, and Murtaugh MP
- Subjects
- Animals, Cluster Analysis, Disease Outbreaks, Evolution, Molecular, Minnesota epidemiology, Molecular Sequence Data, Phylogeny, Porcine respiratory and reproductive syndrome virus pathogenicity, Sequence Homology, Swine, Virulence, Genome, Viral, Porcine Reproductive and Respiratory Syndrome epidemiology, Porcine Reproductive and Respiratory Syndrome virology, Porcine respiratory and reproductive syndrome virus classification, Porcine respiratory and reproductive syndrome virus isolation & purification, RNA, Viral genetics, Sequence Analysis, DNA
- Abstract
In early 2014, a Minnesota sow farm with a solid vaccination history suffered a severe porcine reproductive and respiratory syndrome (PRRS) outbreak with unusually high morbidity and mortality in piglets and sows, as well as anorexia and secondary bacterial infections in nursery pigs. Due to the unusual clinical severity in a PRRS-immune herd, genetic characteristics of the virus were examined to determine if a new PRRSV genotype had emerged. Phylogenetic analysis indicated that the virulent strain (PRRSV2/USA/Minnesota414/2014) was related to virulent strains circulating in the mid-western United States in recent years, and that the nonstructural protein 2 (nsp2) gene of MN414 contained an insertion-deletion pattern typical of existing type 2 virulent strains. We conclude that the MN414 isolate is a recently evolved member of the virulent lineage 1 family of type 2 PRRSV., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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8. Broadly neutralizing antibodies against the rapidly evolving porcine reproductive and respiratory syndrome virus.
- Author
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Robinson SR, Li J, Nelson EA, and Murtaugh MP
- Subjects
- Animals, Cells, Cultured, Cross Protection, Immunoglobulin G blood, Immunoglobulin G immunology, Macrophages, Alveolar virology, Neutralization Tests, Swine, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Antibodies, Viral blood, Antibodies, Viral immunology, Cross Reactions, Porcine Reproductive and Respiratory Syndrome immunology, Porcine respiratory and reproductive syndrome virus immunology
- Abstract
Neutralizing antibodies are a critical part of the immune armory for defense against viruses, and the mechanism by which many effective vaccines work to protect against viral infections. However, infections by rapidly evolving and genetically diverse viruses are often characterized by ineffective neutralizing antibody responses. Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly genetically diverse RNA virus that causes PRRS, the most significant disease of pigs worldwide. The prevailing view of immunity to PRRSV is characterized by delayed and ineffectual production of neutralizing antibodies lacking cross-reactivity that is necessary for vaccine efficacy. Using an ELISA-based neutralizing assay developed to analyze PRRSV growth in porcine alveolar macrophages, the naturally permissive cell of PRRSV, we showed that sera from previously infected commercial sows had high levels of neutralizing activity against diverse PRRSV strains, including across distinct genotypes of PRRSV. Fifty percent cross-neutralization titers in excess of 1/1024 were observed. Neutralizing activity was dose-dependent and was maintained in the immunoglobulin fraction. Presence of high-titer, anti-PRRSV antibody activity that cross-neutralizes diverse strains of virus has prompted reevaluation of the role of neutralizing antibodies for cross-protection against PRRSV under field conditions. Understanding conditions that favor development of cross-neutralizing activity will be crucial for improved strategies to enhance cross-protection against PRRSV. More detailed studies are expected to elucidate mechanisms of neutralizing antibody production and maturation and to investigate conserved epitope targets of cross-neutralization in this rapidly evolving virus., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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9. Full genome sequence analysis of a wild, non-MLV-related type 2 Hungarian PRRSV variant isolated in Europe.
- Author
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Balka G, Wang X, Olasz F, Bálint Á, Kiss I, Bányai K, Rusvai M, Stadejek T, Marthaler D, Murtaugh MP, and Zádori Z
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Europe, Genotype, High-Throughput Nucleotide Sequencing, Hungary, Molecular Sequence Data, Phylogeny, Porcine respiratory and reproductive syndrome virus chemistry, Porcine respiratory and reproductive syndrome virus classification, Porcine respiratory and reproductive syndrome virus genetics, Swine, Viral Proteins chemistry, Viral Proteins genetics, Genome, Viral, Porcine Reproductive and Respiratory Syndrome virology, Porcine respiratory and reproductive syndrome virus isolation & purification
- Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) is a widespread pathogen of pigs causing significant economic losses to the swine industry. The expanding diversity of PRRSV strains makes the diagnosis, control and eradication of the disease more and more difficult. In the present study, the authors report the full genome sequencing of a type 2 PRRSV strain isolated from piglet carcasses in Hungary. Next generation sequencing was used to determine the complete genome sequence of the isolate (PRRSV-2/Hungary/102/2012). Recombination analysis performed with the available full-length genome sequences showed no evidence of such event with other known PRRSV. Unique deletions and an insertion were found in the nsp2 region of PRRSV-2/Hungary/102/2012 when it was compared to the highly virulent VR2332 and JXA-1 prototype strains. The majority of amino acid alterations in GP4 and GP5 of the virus were in the known antigenic regions suggesting an important role for immunological pressure in PRRSV-2/Hungary/102/2012 evolution. Phylogenetic analysis revealed that it belongs to lineage 1 or 2 of type 2 PRRSV. Considering the lack of related PRRSV in Europe, except for a partial sequence from Slovakia, the ancestor of PRRSV-2/Hungary/102/2012 was most probably transported from North-America. It is the first documented type 2 PRRSV isolated in Europe that is not related to the Ingelvac MLV., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
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10. Purifying selection in porcine reproductive and respiratory syndrome virus ORF5a protein influences variation in envelope glycoprotein 5 glycosylation.
- Author
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Robinson SR, Abrahante JE, Johnson CR, and Murtaugh MP
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- Amino Acid Sequence, Animals, Antibodies, Viral immunology, Base Sequence, DNA, Viral genetics, Genome, Viral genetics, Glycosylation, Open Reading Frames genetics, Selection, Genetic, Sequence Analysis, DNA, Swine, Viral Envelope Proteins immunology, Porcine Reproductive and Respiratory Syndrome immunology, Porcine Reproductive and Respiratory Syndrome virology, Porcine respiratory and reproductive syndrome virus genetics, Porcine respiratory and reproductive syndrome virus immunology, Viral Envelope Proteins genetics
- Abstract
Porcine reproductive and respiratory syndrome virus ORF5a protein is encoded in an alternate open reading frame upstream of the major envelope glycoprotein (GP5) in subgenomic mRNA5. Bioinformatic analysis of 3466 type 2 PRRSV sequences showed that the two proteins have co-evolved through a fine balance of purifying codon usage to maintain a conserved RQ-rich motif in ORF5a protein, while eliciting a variable N-linked glycosylation motif in the alternative GP5 reading frame. Conservation of the ORF5a protein RQ-motif also explains an anomalous uracil desert in GP5 hypervariable glycosylation region. The N-terminus of the mature GP5 protein was confirmed to start with amino acid 32, the hypervariable region of the ectodomain. Since GP5 glycosylation variability is assumed to result from immunological selection against neutralizing antibodies, these findings show that an alternative possibility unrelated to immunological selection not only exists, but provides a foundation for investigating previously unsuspected aspects of PRRSV biology. Understanding functional consequences of subtle nucleotide sequence modifications in the region responsible for critical function in ORF5a protein and GP5 glycosylation is essential for rational design of new vaccines against PRRS., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2013
- Full Text
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11. Cellular pathogenesis of porcine circovirus type 2 infection.
- Author
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Dvorak CM, Puvanendiran S, and Murtaugh MP
- Subjects
- Animals, Cell Line, Swine, Viral Load, Virus Cultivation methods, Apoptosis, Circovirus growth & development, Circovirus pathogenicity, Cytopathogenic Effect, Viral
- Abstract
Porcine circovirus associated disease (PCVAD) and the associated histological lesions are thought to appear due to an increase in the amount of porcine circovirus type 2 (PCV2) present in an infected animal. However, examination of the cellular and molecular pathogenesis of PCVAD is complicated by the lack of a consistent cell culture model that replicates the animal phenotypes of persistent, asymptomatic infection, and acute, pathological disease typified by lymphocyte depletion. The porcine fetal retina cell line, VR1BL, shows a high permissiveness to PCV2 infection, 40 times higher than the alternative PK15 culture model, allowing for high titer viral production, with PCV2b growth higher than PCV2a growth. Cytopathic effect due to apoptosis is observed after challenge with high amounts of PCV2, but at low levels, infection is maintained in passaged cells. Thus, VR1BL cells may be used as a model system to examine both acute viral pathogenesis and cellular innate defense, as well as persistent PCV2 infection., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2013
- Full Text
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12. Immunological solutions for treatment and prevention of porcine reproductive and respiratory syndrome (PRRS).
- Author
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Murtaugh MP and Genzow M
- Subjects
- Animals, Genetic Variation, Porcine respiratory and reproductive syndrome virus classification, Porcine respiratory and reproductive syndrome virus genetics, Swine, United States, Porcine Reproductive and Respiratory Syndrome prevention & control, Porcine Reproductive and Respiratory Syndrome therapy, Porcine respiratory and reproductive syndrome virus immunology, Viral Vaccines administration & dosage, Viral Vaccines immunology
- Abstract
Vaccination is the principal means used to control and treat porcine reproductive and respiratory syndrome virus (PRRSV) infection. An array of PRRS vaccine products is available in various regions of the world. However, despite extensive efforts, little progress has been made to improve efficacy since the first introduction of a live, attenuated vaccine in 1994 in the USA. Key limitations include: (a) uncertainty about the viral targets of protective immunity that prevents a research focus on individual viral structures and proteins, and frustrates efforts to design novel vaccines; (b) inability to establish clear immunological correlates of protection that requires laborious in vivo challenge models for evaluation of protection against challenge; and (c) the great genetic diversity of PRRSV which requires that challenge experiments be interpreted cautiously since it is not possible to predict how immunological protection against one isolate will translate to broadly cross-protective immunity. Economically significant levels of cross-protection that are provided to a variety of field isolates still cannot assure that effective protection will be conferred to isolates that might emerge in the future. In addition to these substantial barriers to new PRRSV vaccine development, there are enormous gaps in our understanding of porcine immunological mechanisms and processes that provide immunity to PRRSV infection and memory responses for long-term protection. Despite these impediments, we should be confident that progress will be made. Sequencing of the swine genome is providing a rich source of primary knowledge of gene structure and transcriptional regulation that is certain to reveal important insights about the mechanisms of anti-PRRSV immunity, and continued efforts to unravel the details of the interaction of PRRSV with pigs will lead to new insights that overcome the current limitations in the field., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
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13. Absence of porcine circovirus type 1 (PCV1) and high prevalence of PCV 2 exposure and infection in swine finisher herds.
- Author
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Puvanendiran S, Stone S, Yu W, Johnson CR, Abrahante J, Jimenez LG, Griggs T, Haley C, Wagner B, and Murtaugh MP
- Subjects
- Animals, Antibodies, Viral blood, Antibodies, Viral immunology, Capsid immunology, Capsid virology, DNA, Viral analysis, Enzyme-Linked Immunosorbent Assay, Linear Models, Plasmids, Polymerase Chain Reaction, Prevalence, Sequence Analysis, DNA, Swine, Swine Diseases epidemiology, Circoviridae Infections epidemiology, Circovirus growth & development, Circovirus pathogenicity, Swine Diseases virology
- Abstract
Porcine circovirus (PCV) appeared in 1974 as an unidentified, innocuous viral inhabitant of cell cultures and pigs. Today PCV1 is a contaminant of some human vaccines, and PCV2 is a major pathogen of swine. PCV1 is reportedly ubiquitous in swine but nonpathogenic. Since the interplay of PCV1 and PCV2 in swine might explain variable disease results and shed light on the potential for human exposure, we analyzed in depth the prevalence of PCV1 and PCV2 infection and exposure in the U.S. finishing swine herd. Over 82% of sera from 185 farms were positive for PCV2 by PCR, whereas only 2.4% were positive for PCV1. More than 80% of PCV2 DNA-positive swine were also positive for anti-PCV2 antibodies. PCV1 was only rarely present. Exposure of swine, and therefore humans via pigs, to PCV1 is negligible. We conclude that PCV2 causes a persistent infection in pigs and that PCV1 is absent or rare in swine., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2011
- Full Text
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14. The ever-expanding diversity of porcine reproductive and respiratory syndrome virus.
- Author
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Murtaugh MP, Stadejek T, Abrahante JE, Lam TT, and Leung FC
- Subjects
- Animals, Genotype, Molecular Epidemiology, Phylogeny, Porcine Reproductive and Respiratory Syndrome immunology, Porcine Reproductive and Respiratory Syndrome pathology, Porcine respiratory and reproductive syndrome virus immunology, Porcine respiratory and reproductive syndrome virus pathogenicity, Selection, Genetic, Swine, Virulence, Genetic Variation, Porcine Reproductive and Respiratory Syndrome epidemiology, Porcine Reproductive and Respiratory Syndrome virology, Porcine respiratory and reproductive syndrome virus classification, Porcine respiratory and reproductive syndrome virus genetics, RNA, Viral genetics
- Abstract
Porcine reproductive and respiratory syndrome (PRRS) virus appeared 20 years ago as the cause of a new disease in swine. Today PRRS is the most significant swine disease worldwide in spite of intensive immunological interventions. The virus showed remarkable genetic variation with two geographically distinct genotypes at the time of its discovery, indicating the possibility of prolonged evolutionary divergence prior to its appearance as a swine pathogen. Since then, both type 1 and type 2 have spread geographically, radiated genetically, and acquired new phenotypic characteristics, especially increased virulence. Here, we explore various hypotheses that might account for rapid expansion and diversification of PRRSV, including mechanisms specific to PRRSV and other arteriviruses, cellular modification processes, and immunological selection. Phylogenetic analysis of PRRSV has provided a broadly applicable means to relate diverse isolates, but it does not explain biological variation in virulence or immunological cross-protection. We present other methods of classification and review their limitations. Major questions about PRRSV remain unanswered despite intensive investigation, suggesting that the interaction of PRRSV with pigs involves novel biological processes that may be relevant to other RNA virus and host interactions., (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
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15. Molecular epidemiology of PRRSV: a phylogenetic perspective.
- Author
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Shi M, Lam TT, Hon CC, Hui RK, Faaberg KS, Wennblom T, Murtaugh MP, Stadejek T, and Leung FC
- Subjects
- Animals, Cluster Analysis, Evolution, Molecular, Genetic Variation, Molecular Epidemiology, Porcine Reproductive and Respiratory Syndrome transmission, Porcine respiratory and reproductive syndrome virus genetics, RNA, Viral genetics, Recombination, Genetic, Swine, Porcine Reproductive and Respiratory Syndrome epidemiology, Porcine Reproductive and Respiratory Syndrome virology, Porcine respiratory and reproductive syndrome virus classification, Porcine respiratory and reproductive syndrome virus isolation & purification
- Abstract
Since its first discovery two decades ago, porcine reproductive and respiratory syndrome virus (PRRSV) has been the subject of intensive research due to its huge impact on the worldwide swine industry. Thanks to the phylogenetic analyses, much has been learned concerning the genetic diversity and evolution history of the virus. In this review, we focused on the evolutionary and epidemiological aspects of PRRSV from a phylogenetic perspective. We first described the diversity and transmission dynamics of Type 1 and 2 PRRSV, respectively. Then, we focused on the more ancient evolutionary history of PRRSV: the time of onset of all existing PRRSV and an origin hypothesis were discussed. Finally, we summarized the results from previous recombination studies to assess the potential impact of recombination on the virus epidemiology., (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
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16. Species specialization in cytokine biology: is interleukin-4 central to the T(H)1-T(H)2 paradigm in swine?
- Author
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Murtaugh MP, Johnson CR, Xiao Z, Scamurra RW, and Zhou Y
- Subjects
- Animals, Antibody Formation immunology, B-Lymphocytes metabolism, B-Lymphocytes pathology, Cell Differentiation, Cell Proliferation, Communicable Diseases immunology, Epitopes, Gene Knockout Techniques, Humans, Immunity, Cellular, Interleukin-4 metabolism, Mice, Species Specificity, Th1 Cells metabolism, Th1 Cells pathology, Th2 Cells metabolism, Th2 Cells pathology, B-Lymphocytes immunology, Interleukin-4 immunology, Swine immunology, Th1 Cells immunology, Th2 Cells immunology
- Abstract
The TH1-TH2 paradigm provides an elegant model of directed response to infectious pathogens. Developed in the mouse, the model has provided a framework for systematic and mechanistic studies of immune regulation, protective immunity, and vaccine development in swine. Interleukin-4 (IL-4) plays a central role in the paradigm as a regulatory molecule directing development of the TH2 phenotype, as a developmental cytokine essential for antibody production, and as a soluble diagnostic marker of the TH2 cell type. In contrast, while characterizing the biological properties of porcine IL-4, we discovered that it was not a stimulatory factor for porcine B cells. Rather, it blocked antibody and IL-6 secretion and suppressed antigen-stimulated proliferation of B cells. Inhibition was not reversed by treatment with IL-2 and IL-6 treatment. IL-4 did not stimulate T lymphocyte proliferation, but induced cell growth in lymphoblasts in a dose-dependent fashion. These results suggest that IL-4 plays a different role in pigs than in mice and humans, in which it stimulates B cells and is essential for antibody production. Furthermore, the functions of IL-4 in swine cannot be inferred from results in model systems such as the mouse. General models of disease resistance show substantial variation between pigs and mice at the cellular and molecular level. Advances in somatic cell technologies and animal engineering to enable gene knockouts in pigs, in combination with a continuously expanding immunological toolkit, promise an exciting future for pig immunology, detailed mechanistic elucidation of the TH1-TH2 paradigm, and an improved understanding of the role of IL-4 in porcine immunity to infectious disease.
- Published
- 2009
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17. Impact of a modified-live porcine reproductive and respiratory syndrome virus vaccine intervention on a population of pigs infected with a heterologous isolate.
- Author
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Cano JP, Dee SA, Murtaugh MP, and Pijoan C
- Subjects
- Animals, Porcine Reproductive and Respiratory Syndrome immunology, Porcine Reproductive and Respiratory Syndrome physiopathology, Porcine Reproductive and Respiratory Syndrome virology, Porcine respiratory and reproductive syndrome virus immunology, Porcine respiratory and reproductive syndrome virus isolation & purification, RNA, Viral blood, Swine, Viral Load, Viral Vaccines genetics, Viral Vaccines immunology, Viremia immunology, Viremia prevention & control, Viremia virology, Virulence, Antibodies, Viral blood, Porcine Reproductive and Respiratory Syndrome prevention & control, Porcine respiratory and reproductive syndrome virus classification, Porcine respiratory and reproductive syndrome virus pathogenicity, Vaccination veterinary, Viral Vaccines administration & dosage
- Abstract
The objectives of this study were to evaluate the effects of a therapeutic vaccine intervention with a modified-live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine on the dynamics of a heterologous viral infection in a population of pigs, and to determine the clinical and virological response of previously exposed and vaccinated pigs against a second virulent heterologous challenge. A population of 320 pigs were infected with a field isolate, PRRSV MN-30100, alone or followed by Ingelvac PRRS MLV vaccine administered one to three times at 30 days intervals beginning 1 week after infection. Vaccine intervention reduced the duration of viral shedding, but did not reduce the viral load in tissues or the proportion of persistently infected pigs. A different and highly virulent field isolate, MN-184, was then given as a heterologous viral challenge at 97 days after first exposure. Previously infected and vaccinated pigs showed a significant reduction in clinical signs and enhanced weight gain after the highly virulent challenge with PRRSV MN-184, but infection with and shedding of the challenge isolate were not prevented.
- Published
- 2007
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18. Characterization of heteroclite subgenomic RNAs associated with PRRSV infection.
- Author
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Yuan S, Murtaugh MP, Schumann FA, Mickelson D, and Faaberg KS
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Blotting, Northern, Cell Line, Centrifugation, Density Gradient, DNA, Complementary chemistry, Haplorhini, Molecular Sequence Data, Porcine respiratory and reproductive syndrome virus genetics, RNA, Viral metabolism, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Terminal Repeat Sequences, Transcription, Genetic, Virus Assembly, Porcine respiratory and reproductive syndrome virus isolation & purification, Porcine respiratory and reproductive syndrome virus physiology, RNA, Viral genetics, RNA, Viral isolation & purification, Virion chemistry
- Abstract
In this study, porcine reproductive and respiratory syndrome virus (PRRSV) heteroclite (uncommon forms) RNAs were characterized. Nucleotide sequencing of 11 additional defective RNA species verified that heteroclites are formed between the 5' and 3' termini of PRRSV at short stretches of identity, with variability seen between the junction sites utilized. Northern blot and RT-PCR analyses indicated that heteroclite RNA species were likely to be packaged into purified virions. To study whether heteroclite RNAs and viral genomic RNAs could be packaged into the same virions, PRRSV strain VR-2332 was purified by sucrose density gradient centrifugation. RT-PCR amplification of the viral RNAs isolated from three distinct gradient bands, using genomic- and heteroclite-specific primer pairs, demonstrated that heteroclite RNAs could not be readily dissociated from genomic RNA. Partial segregation of full-length and larger heteroclite genomes to the upper two gradient bands was seen, but smaller species could be found in all three fractions. These results strongly suggest that heteroclite RNAs retain the PRRSV RNA packaging signal. In vitro transcription and translation of one heteroclite cDNA clone verified that the RNA could express a predicted 32.6 kDa protein, indicating that these RNA species have the potential to produce abnormal proteins in infected cells.
- Published
- 2004
- Full Text
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