Special Issue "Genomics of Avian Viral Infections"

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Animal Genetics and Genomics".

Deadline for manuscript submissions: 5 October 2021.

Special Issue Editor

Dr. Jacqueline Smith
E-Mail Website
Guest Editor
The Royal (Dick) School of Veterinary Studies and The Roslin Institute Easter Bush Campus, Midlothian, EH25 9RG, Edinburgh, UK
Interests: avian genomics; chickens; host responses to infection; disease resistance; avian influenza; Marek’s Disease; environmental adaptation
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

The poultry industry currently accounts for the production of around 118 million metric tons of meat and around 74 million metric tons of eggs annually. As the global population continues to increase, so does our reliance on poultry as a food source. It is therefore of vital importance that we safeguard this valuable resource and make the industry as economically competitive as possible. Avian viral infections, however, continue to cost the poultry industry billions of dollars annually. This can be in terms of vaccination costs, loss of birds and decreased production. With a view to improving the health and welfare of commercial birds and to minimising associated economic losses, it is therefore of great importance that we try to understand the genetic mechanisms underlying host susceptibility and resilience to some of the major viral pathogens that threaten the poultry species. Some avian viruses, through their zoonotic potential, also pose a risk to human health. This Special Issue will present papers that describe our current knowledge on host responses to various viral pathogens, the genetics underlying those responses and how genomics can begin to provide a solution for resolving the threat posed by these infections.

Dr. Jacqueline Smith
Guest Editor

Manuscript Submission Information

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Keywords

  • Avian genomics
  • Avian influenza (AI)
  • Candidate genes
  • Chicken
  • Genetics
  • Infectious Bronchitis Virus (IBV)
  • Infectious Bursal Disease Virus (IBDV)
  • Marek’s Disease Virus (MDV)
  • Newcastle Disease Virus (NDV)
  • Poultry
  • Quantitative Trait Loci (QTL)
  • Resistance
  • Single Nucleotide Polymorphism (SNP)
  • Vaccines
  • Viral load

Published Papers (11 papers)

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Editorial

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Editorial
Genomics of Avian Viral Infections
Genes 2019, 10(10), 814; https://doi.org/10.3390/genes10100814 - 15 Oct 2019
Cited by 2 | Viewed by 894
Abstract
The poultry industry currently accounts for the production of around 118 million metric tons of meat and around 74 million metric tons of eggs annually. As the global population continues to increase, so does our reliance on poultry as a food source. It [...] Read more.
The poultry industry currently accounts for the production of around 118 million metric tons of meat and around 74 million metric tons of eggs annually. As the global population continues to increase, so does our reliance on poultry as a food source. It is therefore of vital importance that we safeguard this valuable resource and make the industry as economically competitive as possible. Avian viral infections, however, continue to cost the poultry industry billions of dollars annually. This can be in terms of vaccination costs, loss of birds and decreased production. With a view to improving the health and welfare of commercial birds and to minimizing associated economic losses, it is therefore of great importance that we try to understand the genetic mechanisms underlying host susceptibility and resilience to some of the major viral pathogens that threaten the poultry species. Some avian viruses, through their zoonotic potential, also pose a risk to human health. This Special Issue will present papers that describe our current knowledge on host responses to various viral pathogens, the genetics underlying those responses and how genomics can begin to provide a solution for resolving the threat posed by these infections. Full article
(This article belongs to the Special Issue Genomics of Avian Viral Infections)

Research

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Article
A Homeostasis Hypothesis of Avian Influenza Resistance in Chickens
Genes 2019, 10(7), 543; https://doi.org/10.3390/genes10070543 - 17 Jul 2019
Cited by 2 | Viewed by 1442
Abstract
Avian influenza has caused significant damage to the poultry industry globally. Consequently, efforts have been made to elucidate the disease mechanisms as well as the mechanisms of disease resistance. Here, by investigating two chicken breeds with distinct responses to avian influenza virus (AIV), [...] Read more.
Avian influenza has caused significant damage to the poultry industry globally. Consequently, efforts have been made to elucidate the disease mechanisms as well as the mechanisms of disease resistance. Here, by investigating two chicken breeds with distinct responses to avian influenza virus (AIV), Leghorn GB2 and Fayoumi M43, we compared their genome, methylation, and transcriptome differences. MX1, HSP90AB1, and HSP90B1 exhibited high degrees of genetic differentiation (FST) between the two species. Except for the MX1-involved direct anti-virus mechanism, we found that at the methylation and transcriptome levels, the more AIV-resistant breed, Fayoumi, exhibited less variation compared with Leghorn after AIV inoculation, which included change trends in differentially expressed regions, top-fold change genes with FDR-corrected p < 0.05, immune response related genes, and housekeeping genes. Fayoumi also showed better consistency regarding changes in methylation and changes at the transcriptome level. Our results suggest a homeostasis hypothesis for avian influenza resistance, with Fayoumi maintaining superior homeostasis at both the epigenetic and gene expression levels. Three candidate genes—MX1, HSP90AB1, and HSP90B1—showed genetic differentiation and altered gene expression, methylation, and protein expression, which merit attention in further functional studies. Full article
(This article belongs to the Special Issue Genomics of Avian Viral Infections)
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Article
Chicken Embryonic-Stem Cells Are Permissive to Poxvirus Recombinant Vaccine Vectors
Genes 2019, 10(3), 237; https://doi.org/10.3390/genes10030237 - 20 Mar 2019
Cited by 4 | Viewed by 2726
Abstract
The discovery of mammalian pluripotent embryonic stem cells (ESC) has revolutionised cell research and regenerative medicine. More recently discovered chicken ESC (cESC), though less intensively studied, are increasingly popular as vaccine substrates due to a dearth of avian cell lines. Information on the [...] Read more.
The discovery of mammalian pluripotent embryonic stem cells (ESC) has revolutionised cell research and regenerative medicine. More recently discovered chicken ESC (cESC), though less intensively studied, are increasingly popular as vaccine substrates due to a dearth of avian cell lines. Information on the comparative performance of cESC with common vaccine viruses is limited. Using RNA-sequencing, we compared cESC transcriptional programmes elicited by stimulation with chicken type I interferon or infection with vaccine viruses routinely propagated in primary chicken embryo fibroblasts (CEF). We used poxviruses (fowlpox virus (FWPV) FP9, canarypox virus (CNPV), and modified vaccinia virus Ankara (MVA)) and a birnavirus (infectious bursal disease virus (IBDV) PBG98). Interferon-stimulated genes (ISGs) were induced in cESC to levels comparable to those in CEF and immortalised chicken fibroblast DF-1 cells. cESC are permissive (with distinct host transcriptional responses) to MVA, FP9, and CNPV but, surprisingly, not to PBG98. MVA, CNPV, and FP9 suppressed innate immune responses, while PBG98 induced a subset of ISGs. Dysregulation of signalling pathways (i.e., NFκB, TRAF) was observed, which might affect immune responses and viral replication. In conclusion, we show that cESC are an attractive alternative substrate to study and propagate poxvirus recombinant vaccine vectors. Full article
(This article belongs to the Special Issue Genomics of Avian Viral Infections)
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Article
Dynamic Expression of Interferon Lambda Regulated Genes in Primary Fibroblasts and Immune Organs of the Chicken
Genes 2019, 10(2), 145; https://doi.org/10.3390/genes10020145 - 14 Feb 2019
Cited by 6 | Viewed by 1656
Abstract
Interferons (IFNs) are pleiotropic cytokines that establish a first line of defense against viral infections in vertebrates. Several types of IFN have been identified; however, limited information is available in poultry, especially using live animal experimental models. IFN-lambda (IFN-λ) has recently been shown [...] Read more.
Interferons (IFNs) are pleiotropic cytokines that establish a first line of defense against viral infections in vertebrates. Several types of IFN have been identified; however, limited information is available in poultry, especially using live animal experimental models. IFN-lambda (IFN-λ) has recently been shown to exert a significant antiviral impact against viral pathogens in mammals. In order to investigate the in vivo potential of chicken IFN-λ (chIFN-λ) as a regulator of innate immunity, and potential antiviral therapeutics, we profiled the transcriptome of chIFN-λ-stimulated chicken immune organs (in vivo) and compared it with primary chicken embryo fibroblasts (in vitro). Employing the baculovirus expression vector system (BEVS), recombinant chIFN-λ3 (rchIFN-λ3) was produced and its biological activities were demonstrated. The rchIFNλ3 induced a great array of IFN-regulated genes in primary chicken fibroblast cells. The transcriptional profiling using RNA-seq and subsequent bioinformatics analysis (gene ontology, differential expressed genes, and KEGGs analysis) of the bursa of Fabricious and the thymus demonstrated an upregulation of crucial immune genes (viperin, IKKB, CCL5, IL1β, and AP1) as well as the antiviral signaling pathways. Interestingly, this experimental approach revealed contrasting evidence of the antiviral potential of chIFN-λ in both in vivo and in vitro models. Taken together, our data signifies the potential of chIFN-λ as a potent antiviral cytokine and highlights its future possible use as an antiviral therapeutic in poultry. Full article
(This article belongs to the Special Issue Genomics of Avian Viral Infections)
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Article
Comparison of the Transcriptomes and Proteomes of Serum Exosomes from Marek’s Disease Virus-Vaccinated and Protected and Lymphoma-Bearing Chickens
Genes 2019, 10(2), 116; https://doi.org/10.3390/genes10020116 - 05 Feb 2019
Cited by 13 | Viewed by 1925
Abstract
Marek’s disease virus (MDV) is the causative agent of Marek’s disease (MD), a complex pathology of chickens characterized by paralysis, immunosuppression, and T-cell lymphomagenesis. MD is controlled in poultry production via vaccines administered in ovo or at hatch, and these confer protection against [...] Read more.
Marek’s disease virus (MDV) is the causative agent of Marek’s disease (MD), a complex pathology of chickens characterized by paralysis, immunosuppression, and T-cell lymphomagenesis. MD is controlled in poultry production via vaccines administered in ovo or at hatch, and these confer protection against lymphoma formation, but not superinfection by MDV field strains. Despite vaccine-induced humoral and cell-mediated immune responses, mechanisms eliciting systemic protection remain unclear. Here we report the contents of serum exosomes to assess their possible roles as indicators of systemic immunity, and alternatively, tumor formation. We examined the RNA and protein content of serum exosomes from CVI988 (Rispens)-vaccinated and protected chickens (VEX), and unvaccinated tumor-bearing chickens (TEX), via deep-sequencing and mass spectrometry, respectively. Bioinformatic analyses of microRNAs (miRNAs) and predicted miRNA targets indicated a greater abundance of tumor suppressor miRNAs in VEX compared to TEX. Conversely, oncomiRs originating from cellular (miRs 106a-363) and MDV miRNA clusters were more abundant in TEX compared to VEX. Most notably, mRNAs mapping to the entire MDV genome were identified in VEX, while mRNAs mapping to the repeats flanking the unique long (IRL/TRL) were identified in TEX. These data suggest that long-term systemic vaccine-induced immune responses may be mediated at the level of VEX which transfer viral mRNAs to antigen presenting cells systemically. Proteomic analyses of these exosomes suggested potential biomarkers for VEX and TEX. These data provide important putative insight into MDV-mediated immune suppression and vaccine responses, as well as potential serum biomarkers for MD protection and susceptibility. Full article
(This article belongs to the Special Issue Genomics of Avian Viral Infections)
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Article
Impact of HVT Vaccination on Splenic miRNA Expression in Marek’s Disease Virus Infections
Genes 2019, 10(2), 115; https://doi.org/10.3390/genes10020115 - 05 Feb 2019
Cited by 4 | Viewed by 1283
Abstract
Marek’s Disease is a lymphoproliferative disease of chickens caused by Marek’s Disease Virus. Similar to other herpesviruses, Marek’s Disease Virus (MDV) encodes its own small non-coding regulatory RNAs termed microRNAs (miRNAs). We previously found that the expression profile of these viral miRNAs is [...] Read more.
Marek’s Disease is a lymphoproliferative disease of chickens caused by Marek’s Disease Virus. Similar to other herpesviruses, Marek’s Disease Virus (MDV) encodes its own small non-coding regulatory RNAs termed microRNAs (miRNAs). We previously found that the expression profile of these viral miRNAs is affected by vaccination with Herpesvirus of Turkeys (HVT). To further characterize miRNA-mediated gene regulation in MDV infections, in the current study we examine the impact of HVT vaccination on cellular miRNA expression in MDV-infected specific-pathogen-free (SPF) chickens. We used small RNA-seq to identify 24 cellular miRNAs that exhibited altered splenic expression in MDV infected chickens (42 dpi) compared to age-matched uninfected birds. We then used Real Time-quantitative PCR (RT-qPCR) to develop expression profiles of a select group of these host miRNAs in chickens receiving the HVT vaccine and in vaccinated chickens subsequently infected with MDV. As was seen with viral miRNA, host miRNAs had unique splenic expression profiles between chickens infected with HVT, MDV, or co-infected birds. We also discovered a group of transcription factors, using a yeast one-hybrid screen, which regulates immune responses and cell growth pathways and also likely regulates the expression of these cellular miRNAs. Overall, this study suggests cellular miRNAs are likely a critical component of both protection from and progression of Marek’s Disease. Full article
(This article belongs to the Special Issue Genomics of Avian Viral Infections)
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Article
Macrophages from Susceptible and Resistant Chicken Lines have Different Transcriptomes following Marek’s Disease Virus Infection
Genes 2019, 10(2), 74; https://doi.org/10.3390/genes10020074 - 22 Jan 2019
Cited by 9 | Viewed by 2095
Abstract
Despite successful control by vaccination, Marek’s disease (MD) has continued evolving to greater virulence over recent years. To control MD, selection and breeding of MD-resistant chickens might be a suitable option. MHC-congenic inbred chicken lines, 61 and 72, are highly [...] Read more.
Despite successful control by vaccination, Marek’s disease (MD) has continued evolving to greater virulence over recent years. To control MD, selection and breeding of MD-resistant chickens might be a suitable option. MHC-congenic inbred chicken lines, 61 and 72, are highly resistant and susceptible to MD, respectively, but the cellular and genetic basis for these phenotypes is unknown. Marek’s disease virus (MDV) infects macrophages, B-cells, and activated T-cells in vivo. This study investigates the cellular basis of resistance to MD in vitro with the hypothesis that resistance is determined by cells active during the innate immune response. Chicken bone marrow-derived macrophages from lines 61 and 72 were infected with MDV in vitro. Flow cytometry showed that a higher percentage of macrophages were infected in line 72 than in line 61. A transcriptomic study followed by in silico functional analysis of differentially expressed genes was then carried out between the two lines pre- and post-infection. Analysis supports the hypothesis that macrophages from susceptible and resistant chicken lines display a marked difference in their transcriptome following MDV infection. Resistance to infection, differential activation of biological pathways, and suppression of oncogenic potential are among host defense strategies identified in macrophages from resistant chickens. Full article
(This article belongs to the Special Issue Genomics of Avian Viral Infections)
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Article
Genetics and Genomic Regions Affecting Response to Newcastle Disease Virus Infection under Heat Stress in Layer Chickens
Genes 2019, 10(1), 61; https://doi.org/10.3390/genes10010061 - 18 Jan 2019
Cited by 8 | Viewed by 1998
Abstract
Newcastle disease virus (NDV) is a highly contagious avian pathogen that poses a tremendous threat to poultry producers in endemic zones due to its epidemic potential. To investigate host genetic resistance to NDV while under the effects of heat stress, a genome-wide association [...] Read more.
Newcastle disease virus (NDV) is a highly contagious avian pathogen that poses a tremendous threat to poultry producers in endemic zones due to its epidemic potential. To investigate host genetic resistance to NDV while under the effects of heat stress, a genome-wide association study (GWAS) was performed on Hy-Line Brown layer chickens that were challenged with NDV while under high ambient temperature to identify regions associated with host viral titer, circulating anti-NDV antibody titer, and body weight change. A single nucleotide polymorphism (SNP) on chromosome 1 was associated with viral titer at two days post-infection (dpi), while 30 SNPs spanning a quantitative trait loci (QTL) on chromosome 24 were associated with viral titer at 6 dpi. Immune related genes, such as CAMK1d and CCDC3 on chromosome 1, associated with viral titer at 2 dpi, and TIRAP, ETS1, and KIRREL3, associated with viral titer at 6 dpi, were located in two QTL regions for viral titer that were identified in this study. This study identified genomic regions and candidate genes that are associated with response to NDV during heat stress in Hy-Line Brown layer chickens. Regions identified for viral titer on chromosome 1 and 24, at 2 and 6 dpi, respectively, included several genes that have key roles in regulating the immune response. Full article
(This article belongs to the Special Issue Genomics of Avian Viral Infections)
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Article
Integrated Proteomic and Transcriptomic Analysis of Differential Expression of Chicken Lung Tissue in Response to NDV Infection during Heat Stress
Genes 2018, 9(12), 579; https://doi.org/10.3390/genes9120579 - 27 Nov 2018
Cited by 9 | Viewed by 1655
Abstract
Newcastle disease virus (NDV) is a devastating worldwide poultry pathogen with major implications for global food security. In this study, two highly inbred and genetically distinct chicken lines, Fayoumis and Leghorns, were exposed to a lentogenic strain of NDV, while under the effects [...] Read more.
Newcastle disease virus (NDV) is a devastating worldwide poultry pathogen with major implications for global food security. In this study, two highly inbred and genetically distinct chicken lines, Fayoumis and Leghorns, were exposed to a lentogenic strain of NDV, while under the effects of heat stress, in order to understand the genetic mechanisms of resistance during high ambient temperatures. Fayoumis, which are relatively more resistant to pathogens than Leghorns, had larger numbers of differentially expressed genes (DEGs) during the early stages of infection when compared to Leghorns and subsequently down-regulated their immune response at the latter stages to return to homeostasis. Leghorns had very few DEGs across all observed time points, with the majority of DEGs involved with metabolic and glucose-related functions. Proteomic analysis corroborates findings made within Leghorns, while also identifying interesting candidate genes missed by expression profiling. Poor correlation between changes observed in the proteomic and transcriptomic datasets highlights the potential importance of integrative approaches to understand the mechanisms of disease response. Overall, this study provides novel insights into global protein and expression profiles of these two genetic lines, and provides potential genetic targets involved with NDV resistance during heat stress in poultry. Full article
(This article belongs to the Special Issue Genomics of Avian Viral Infections)
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Article
Association of Candidate Genes with Response to Heat and Newcastle Disease Virus
Genes 2018, 9(11), 560; https://doi.org/10.3390/genes9110560 - 19 Nov 2018
Cited by 4 | Viewed by 1726
Abstract
Newcastle disease is considered the number one disease constraint to poultry production in low and middle-income countries, however poultry that is raised in resource-poor areas often experience multiple environmental challenges. Heat stress has a negative impact on production, and immune response to pathogens [...] Read more.
Newcastle disease is considered the number one disease constraint to poultry production in low and middle-income countries, however poultry that is raised in resource-poor areas often experience multiple environmental challenges. Heat stress has a negative impact on production, and immune response to pathogens can be negatively modulated by heat stress. Candidate genes and regions chosen for this study were based on previously reported associations with response to immune stimulants, pathogens, or heat, including: TLR3, TLR7, MX, MHC-B (major histocompatibility complex, gene complex), IFI27L2, SLC5A1, HSPB1, HSPA2, HSPA8, IFRD1, IL18R1, IL1R1, AP2A2, and TOLLIP. Chickens of a commercial egg-laying line were infected with a lentogenic strain of NDV (Newcastle disease virus); half the birds were maintained at thermoneutral temperature and the other half were exposed to high ambient temperature before the NDV challenge and throughout the remainder of the study. Phenotypic responses to heat, to NDV, or to heat + NDV were measured. Selected SNPs (single nucleotide polymorphisms) within 14 target genes or regions were genotyped; and genotype effects on phenotypic responses to NDV or heat + NDV were tested in each individual treatment group and the combined groups. Seventeen significant haplotype effects, among seven genes and seven phenotypes, were detected for response to NDV or heat or NDV + heat. These findings identify specific genetic variants that are associated with response to heat and/or NDV which may be useful in the genetic improvement of chickens to perform favorably when faced with pathogens and heat stress. Full article
(This article belongs to the Special Issue Genomics of Avian Viral Infections)
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Other

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Erratum
Erratum: Chakraborty, P. et al. Macrophages from Susceptible and Resistant Chicken Lines have Different Transcriptomes following Marek’s Disease Virus Infection. Genes 2019, 10, 74
Genes 2020, 11(7), 796; https://doi.org/10.3390/genes11070796 - 15 Jul 2020
Cited by 1 | Viewed by 504
Abstract
The authors wish to make the following correction to their paper published in Genes [...] Full article
(This article belongs to the Special Issue Genomics of Avian Viral Infections)

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Differential miRNA expression profiling of HPAI H5N1 infected chicken lungs reveals critical biological pathways involved in molecular pathogenesis

Abstract: Avian influenza is a highly contagious viral infection mainly affecting the avian species. H5N1 virus has a high capacity for genetic changes making it difficult to control the disease. MicroRNAs are small, regulatory, endogenous, non-coding RNAs of ~22 nucleotides in length which regulate the gene expression by binding to 3' untranslated region (UTR), 5’ UTR or ORF of their target mRNAs. miRNAs play important roles in many of the biological processes and critical in understanding host-pathogen interaction. In the present study, we sequenced the of miRNAs expressed in lungs of specific pathogen free(SPF) chicken infected with avian influenza virus H5N1 on SOLiD platform. The differentially expressed miRNAs during H5N1as compared to non infected  SPF chicken lungs were identified. The top 10 upregulated and downregulated miRNAs were validated by qPCR. The target genes of the differentially expressed miRNAs were predicted by in-silico approach. The target genes of significantly upregulated and downregulated miRNAs were subjected to gene ontology analysis. The analysis has shown that many of the important genes and pathways like Jak-STAT pathway, RIG-I-like receptor signalling pathway, Toll-like receptor signalling pathway, RNA transport, MAPK signalling pathway of the host were affected by the miRNAs expressed in the lungs in response to H5N1 infection. GO terms related to immunity, transcription, protein, signalling pathways, apoptosis etc. were found to be enriched in the analysis. Our study has revealed the molecular pathogenesis that happens in the host after the viral entry. This helps in better understanding of the disease and can be used for devising suitable control strategies against H5N1.

Keywords: H5N1; miRNA; SOLiD; qPCR; Gene ontology

 

Title: Characterisation of Interferon-inducible transmembrane protein expression in infectious bronchitis virus (IBV) infection

Abstract: The coronaviruses encompass a group of enveloped RNA viruses that are widespread in nature and infect a wide variety of animals as well as humans, most commonly causing gastrointestinal or respiratory illnesses in the infected host. Infectious bronchitis virus is a highly pathogenic respiratory pathogen of chickens that can also affect the kidneys and reproductive systems resulting in bird mortality and decreased reproductively. The interferon-inducible transmembrane (IFITM) proteins are activated in response to viral infections and represent a class of cellular restriction factors that block the replication of many viral pathogens. Little is known about the possible role IFITMs play in the restriction of IBV replication. Here, we characterize the relative mRNA expression of the chicken IFITM genes in response to IBV infection, both in-vivo, ex-vivo and in-vitro with the pathogenic M41-CK IBV, the nephropathogenic QX strain and non-pathogenic Beaudette. Using quantitative PCR (qPCR), we demonstrate a significant upregulation of chIFITM1, 2, 3 and 5 in M41-CK and QX infected trachea 2 days post infection. chIFITM10 was found to be significantly upregulated (~50 fold) in M41-CK infected kidney only. We did not observe significant chIFITM mRNA upregulation in trachea infected with Beaudette and found no evidence of active replication of this strain in-vivo. Interestingly, in ex-vivo Tracheal Organ Culture (TOCs) and in-vitro, the replication of Beaudette elicits a significant upregulation of chIFITM1, 2 and 3 at 24-hour post infection. Furthermore, we show that in-vitro infection with M41-CK and QX results in a significant upregulation of chIFITM1, 2 and 3 24 hours post infection. The overexpression of chIFITM2 significantly reduces IBV viral titers and its transient knockdown renders DF-1s more susceptible to IBV infection.  In summary, we confirmed a differential innate response following infection with distinct IBV strains and believe that our data provide new insights into the possible role of chIFITMs in early IBV infection.

 

Title: Comparison of the Transcriptomes and Proteomes of Serum Exosomes from Marek’s Disease Virus-vaccinated and Protected and Lymphoma-bearing Chickens

Authors: Sabari Nath Neerukonda1, Phaedra Tavlarides-Hontz1, Fiona McCarthy2, Kenneth Pendarvis2, and Mark S. Parcells1*

Department of Animal and Food Sciences, University of Delaware, Newark DE

2 Department of Animal and Comparative Biomedical Sciences, The University of Arizona, Tuscon AZ

Abstract: Marek’s disease virus (MDV) is the causative agent of Marek’s disease (MD), a complex pathology of chickens characterized by paralysis, immunosuppression, and T-cell lymphomagenesis. MD is controlled in poultry production via vaccines administered in ovo or at hatch, and these confer protection against lymphoma formation, but not superinfection by MDV field strains. Despite vaccine-induced humoral and cell-mediated immune responses, mechanisms eliciting systemic protection remain unclear. Here we report the contents of serum exosomes to assess their possible roles as indicators of systemic immunity, and alternatively, tumor formation. We examined the RNA and protein content of serum exosomes from CVI988 (Rispens)-vaccinated and protected chickens (VEX), and unvaccinated tumor-bearing chickens (TEX), via deep-sequencing and mass spectrometry, respectively. Bioinformatic analyses of miRNAs and predicted miRNA targets indicated a greater abundance of tumor suppressor miRNAs in VEX compared to TEX. Conversely, oncomiRs belonging to let-7 and miR-15-16 families, or originating from cellular (106a-363) and MDV-1 miRNA clusters were more abundant in TEX compared to VEX. Proteomic analyses indicated that insulin-like growth factor, acid-labile subunit (IGFALS) and collagen XXII 1- (COL22A1) were consistently identified in VEX, whereas pantetheinase (vanin-1) was consistently identified in TEX. These data provide important potential serum biomarkers for MD protection and susceptibility.

Keywords: Marek’s disease, Lymphoma, Exosomes, Pantetheinase, Vanin-1, Insulin-like growth factor, acid labile subunit (IGFALS), COL22A1

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