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Avian Diseases Mar 2019Turkey herpesvirus (HVT) is widely used as a vaccine against Marek's disease in chickens and recently as a vector for foreign genes from infectious bursal disease virus,...
Turkey herpesvirus (HVT) is widely used as a vaccine against Marek's disease in chickens and recently as a vector for foreign genes from infectious bursal disease virus, Newcastle disease (ND) virus, infectious laryngotracheitis (ILT) virus, and avian influenza virus. Advantages of HVT-vector vaccines are that the vaccines do not contain live respiratory viruses or live infectious bursal disease virus able to replicate and cause disease or embryo mortality, they can be administered at hatch or , and they are relatively insensitive to interference from maternally derived antibodies. As producers have tried to combine HVT-vector vaccines to protect against additional diseases, reports have indicated that applying two vectored vaccines using the same HVT vector is reported to reduce the efficacy of one or both vaccines. To confirm this interference, we evaluated commercial vaccines from multiple companies, including products with inserts designed to protect against ND, infectious ILT, and infectious bursal disease (IBD). Using a standard dosage, we found that the ILT product was most severely affected by the addition of other vaccines, as demonstrated by a significant increase in clinical signs, significant decrease in weight gain, and increase in quantity of challenge virus observed from tracheal swabs collected from Days 3-5 postchallenge. The ND and IBD products were also affected by the addition of other vaccines, although in most cases differences compared to vaccination with the vector alone were not statistically significant. This study demonstrates the importance of following manufacturer guidelines and the need for validating alternative strategies to benefit from the high level of protection offered by vector vaccines.
Topics: Animals; Chickens; Genetic Vectors; Herpesvirus 1, Gallid; Herpesvirus 1, Meleagrid; Infectious bursal disease virus; Influenza A virus; Marek Disease; Newcastle disease virus; Poultry Diseases; Vaccination; Vaccines, Combined; Viral Vaccines
PubMed: 31251522
DOI: 10.1637/11979-092818-Reg.1 -
Avian Diseases Dec 2016Shortly after the isolation of Marek's disease (MD) herpesvirus (MDV) in the late 1960s vaccines were developed in England, the United States, and The Netherlands. Biggs... (Review)
Review
Shortly after the isolation of Marek's disease (MD) herpesvirus (MDV) in the late 1960s vaccines were developed in England, the United States, and The Netherlands. Biggs and associates at the Houghton Poultry Research Station (HPRS) in England attenuated HPRS-16, the first cell-culture-isolated MDV strain, by passaging HPRS-16 in chick kidney cells. Although HPRS-16/Att was the first commercially available vaccine, it never became widely used and was soon replaced by the FC126 strain of herpesvirus of turkeys (HVT) vaccine developed by Witter and associates at the Regional Poultry Research Laboratory (now Avian Disease and Oncology Laboratory [ADOL]) in East Lansing, MI. Ironically, Kawamura et al. isolated a herpesvirus from kidney cell cultures from turkeys in 1969 but never realized its potential as a vaccine against MD. Rispens of the Central Veterinary Institute (CVI) developed the third vaccine. His associate, Maas, had found commercial flocks of chickens with MDV antibodies but without MD. Subsequently, Rispens isolated a very low pathogenic strain from hen number 988 from his MD antibody-positive flock, which was free of avian leukosis virus and clinical MD. This isolate became the CVI-988 vaccine used mostly in The Netherlands. During the late 1970s, HVT was no longer fully protective against some new emerging field strains. The addition of SB-1, isolated by Schat and Calnek, to HVT improved protection against the emerging very virulent strains. In the 1990s CVI-988 became the worldwide vaccine gold standard. This review will present data from published papers and personal communications providing additional information about the exciting 15-yr period after the isolation of MDV to the development of the different vaccines.
Topics: Animals; Chickens; Herpesvirus 2, Gallid; Herpesvirus 3, Gallid; History, 20th Century; History, 21st Century; Marek Disease; Marek Disease Vaccines; Poultry Diseases
PubMed: 27902902
DOI: 10.1637/11429-050216-Hist -
Viruses Jul 2023Marek's disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested...
Marek's disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested that MDV suppresses the induction of type I interferons and thus escapes immune control. Cholesterol 25-hydroxylase (CH25H), a gene that encodes an enzyme that catalyses cholesterol to 25-hydroxycholesterol (25-HC), is an interferon-stimulating gene (ISG) known to exert antiviral activities. Other oxysterols, such as 27-hydroxycholesterols (27-HC), have also been shown to exert antiviral activities, and 27-HC is synthesised by the catalysis of cholesterol via the cytochrome P450 enzyme oxidase sterol 27-hydroxylase A1 (CYP27A1). At 24 h post infection (hpi), MDV stimulated a type I interferon (IFN-α) response, which was significantly reduced at 48 and 72 hpi, as detected using the luciferase assay for chicken type I IFNs. Then, using RT-PCR, we demonstrated that chicken type I IFN (IFN-α) upregulates chicken CH25H and CYP27A1 genes in chicken embryo fibroblast (CEF) cells. In parallel, our results demonstrate a moderate and transient upregulation of CH25H at 48 hpi and CYP27A1 at 72hpi in MDV-infected CEF cells. A significant reduction in MDV titer and plaque sizes was observed in CEFs treated with 25-HC or 27-HC in vitro, as demonstrated using a standard plaque assay for MDV. Taken together, our results suggest that 25-HC and 27-HC may be useful antiviral agents to control MDV replication and spread.
Topics: Animals; Chick Embryo; Hydroxycholesterols; Marek Disease; Chickens; Interferon-alpha; Antiviral Agents; Interferon Type I; Virus Replication
PubMed: 37631994
DOI: 10.3390/v15081652 -
Veterinary Journal (London, England :... Sep 2015Gallid herpesvirus-2 (GaHV-2) is an oncogenic α-herpesvirus that causes Marek's disease (MD), a T cell lymphosarcoma (lymphoma) of domestic fowl (chickens). The GaHV-2... (Review)
Review
Gallid herpesvirus-2 (GaHV-2) is an oncogenic α-herpesvirus that causes Marek's disease (MD), a T cell lymphosarcoma (lymphoma) of domestic fowl (chickens). The GaHV-2 genome integrates by homologous recombination into the host genome and, by modulating expression of viral and cellular genes, induces transformation of latently infected cells. MD is a unique model of viral oncogenesis. Mechanisms implicated in the regulation of viral and cellular genes during GaHV-2 infection operate at transcriptional, post-transcriptional and post-translational levels, with involvement of viral and cellular transcription factors, along with epigenetic modifications, alternative splicing, microRNAs and post-translational modifications of viral proteins. Meq, the major oncogenic protein of GaHV-2, is a viral transcription factor that modulates expression of viral genes, for example by binding to the viral bidirectional promoter of the pp38-pp24/1.8 kb mRNA, and also modulates expression of cellular genes, such as Bcl-2 and matrix metalloproteinase 3. GaHV-2 expresses viral telomerase RNA subunit (vTR), which forms a complex with the cellular telomerase reverse transcriptase (TERT), thus contributing to tumorigenesis, while vTR independent of telomerase activity is implicated in metastasis. Expression of a viral interleukin 8 homologue may contribute to lymphomagenesis. Inhibition of expression of the pro-apoptotic factors JARID2 and SMAD2 by viral microRNAs may promote the survival and proliferation of GaHV-2 latently infected cells, thus enhancing tumorigenesis, while inhibition of interleukin 18 by viral microRNAs may be involved in evasion of immune surveillance. Viral envelope glycoproteins derived from glycoprotein B (gp60 and gp49), as well as glycoprotein C, may also play a role in immune evasion.
Topics: Animals; Chickens; Gene Expression Regulation, Viral; Herpesvirus 2, Gallid; Humans; Marek Disease; Poultry Diseases; Virus Latency
PubMed: 26067852
DOI: 10.1016/j.tvjl.2015.04.038 -
Virology Jan 2015Marek׳s disease virus (MDV) is a widespread α-herpesvirus of chickens that causes T cell tumors. Acute, but not latent, MDV infection has previously been shown to lead...
Marek׳s disease virus (MDV) is a widespread α-herpesvirus of chickens that causes T cell tumors. Acute, but not latent, MDV infection has previously been shown to lead to downregulation of cell-surface MHC class I (Virology 282:198-205 (2001)), but the gene(s) involved have not been identified. Here we demonstrate that an MDV gene, MDV012, is capable of reducing surface expression of MHC class I on chicken cells. Co-expression of an MHC class I-binding peptide targeted to the endoplasmic reticulum (bypassing the requirement for the TAP peptide transporter) partially rescued MHC class I expression in the presence of MDV012, suggesting that MDV012 is a TAP-blocking MHC class I immune evasion protein. This is the first unique non-mammalian MHC class I immune evasion gene identified, and suggests that α-herpesviruses have conserved this function for at least 100 million years.
Topics: Amino Acid Sequence; Animals; Antibodies, Viral; Cell Line; Chickens; Gene Expression Regulation; Histocompatibility Antigens Class I; Immune Evasion; Mardivirus; Molecular Sequence Data; Viral Proteins
PubMed: 25462349
DOI: 10.1016/j.virol.2014.11.008 -
Transboundary and Emerging Diseases Jul 2022Marek's disease (MD) is a re-emerging viral disease of chickens and a serious economic threat to the poultry industry worldwide. Continuous surveillance with molecular...
Molecular detection and phylogenetic analysis of Marek's disease virus virulence-associated genes from vaccinated flocks in southern India reveals circulation of virulent MDV genotype.
Marek's disease (MD) is a re-emerging viral disease of chickens and a serious economic threat to the poultry industry worldwide. Continuous surveillance with molecular investigation is essential to monitor the emergence of virulent Marek's disease virus (MDV) strains and to devise any appropriate vaccination strategy and implement bio-security programmes. In the present study, we investigated the cases of MD outbreaks in vaccinated poultry flocks. The MD outbreak was confirmed through necropsy (mainly visceral tumours), histopathology and viral gene specific PCR. The pathotypes of the field MDV strains were assessed by molecular analysis of three virulence-associated genes, meq, pp38 and vIL-8. The Meq sequence of the field strains analyzed in this study lacked the 59 aa unique to mild strains, indicating that they are potentially virulent strains. Mutation at position 71 and the presence of five proline rich repeats in the transactivation domain, both associated with virulence were observed in these strains; however, the signature sequences specific to very virulent plus strains were absent. Phylogenetic analysis of meq oncogene sequences revealed clustering of the field strains with North Indian strains and with a very virulent plus ATE 2539 strain from Hungary. Analyses of pp38 protein at positions 107 and 109 and vIL-8 protein at positions 4 and 31 showed signatures of virulence. Sequence and phylogenetic analysis of oncogene and virulence-associated genes of field MDVs from vaccinated flock indicated that these strains possessed molecular features of virulent strains.
Topics: Animals; Chickens; Genotype; Herpesvirus 2, Gallid; Marek Disease; Phylogeny; Poultry; Poultry Diseases; Virulence
PubMed: 34403565
DOI: 10.1111/tbed.14289 -
Science (New York, N.Y.) Dec 2023The pronounced growth in livestock populations since the 1950s has altered the epidemiological and evolutionary trajectory of their associated pathogens. For example,...
The pronounced growth in livestock populations since the 1950s has altered the epidemiological and evolutionary trajectory of their associated pathogens. For example, Marek's disease virus (MDV), which causes lymphoid tumors in chickens, has experienced a marked increase in virulence over the past century. Today, MDV infections kill >90% of unvaccinated birds, and controlling it costs more than US$1 billion annually. By sequencing MDV genomes derived from archeological chickens, we demonstrate that it has been circulating for at least 1000 years. We functionally tested the oncogene, one of 49 viral genes positively selected in modern strains, demonstrating that ancient MDV was likely incapable of driving tumor formation. Our results demonstrate the power of ancient DNA approaches to trace the molecular basis of virulence in economically relevant pathogens.
Topics: Animals; Chickens; Herpesvirus 2, Gallid; Lymphoma; Marek Disease; Virulence; Phylogeny
PubMed: 38096384
DOI: 10.1126/science.adg2238 -
Veterinary Microbiology Jan 2022The present study was undertaken to quantify the Marek's Disease Virus (MDV) serotypes in vaccinated commercial layer flocks at 7, 14, 21, 28, 35 and 60-90 days post...
The present study was undertaken to quantify the Marek's Disease Virus (MDV) serotypes in vaccinated commercial layer flocks at 7, 14, 21, 28, 35 and 60-90 days post vaccination (dpv) and to correlate the pathogenic Gallid herpesvirus 2 (GaHV-2, MDV1) load with vaccine viral load of Gallid herpesvirus 3 (GaHV-3, MDV2) and Meleagridis herpesvirus 1 (MeHV-1, MDV3). A total of 25 commercial layer flocks were selected in and around Namakkal district of Tamil nadu, India and the feather pulp (FP) and blood samples were collected. Out of 25 flocks, 14 were revaccinated with bivalent vaccine, six were revaccinated with monovalent vaccine apart from the initial bivalent vaccination done at hatchery and five flocks were not revaccinated. SYBR green based real time PCR was used for absolute quantification of MDV serotypes. The pathogenic MDV1 load had shown an increasing trend until 21 dpv followed by a dip and again had shown a constant uptick between 60 and 90 dpv in the flocks that went on to develop MD outbreak. The flocks which had not encountered any Marek's Disease outbreak had shown increasing trend of MDV2 and 3 load until 21 dpv followed by a slight decrease but maintained a higher load when compared to MDV 1 which had marked a sharp decline between 60 and 90 dpv. Outbreak of MD was observed in seven (28%) out of 25 flocks between 18 and 27 weeks of age. It includes, two out of fourteen farms (14%) revaccinated with bivalent vaccine, two out of six farms (33%) revaccinated with MDV3 vaccine and three out of five farms (60%) without revaccination. The overall mean of vaccine viral load at various stages of dpv was constantly low where as pathogenic MDV 1 load was constantly high between 60 and 90 dpv in the flocks that went on to develop Marek's Disease during later part of life.
Topics: Animals; Chickens; Herpesvirus 2, Gallid; India; Marek Disease; Vaccination; Vaccines, Combined
PubMed: 34923248
DOI: 10.1016/j.vetmic.2021.109305 -
Avian Pathology : Journal of the W.V.P.A Feb 2021A double construct vaccine of turkey herpesvirus (HVT) was prepared that contains the fusion (F) gene from Newcastle disease virus (NDV) and the viral protein 2 (VP2)...
Efficacy of a turkey herpesvirus double construct vaccine (HVT-ND-IBD) against challenge with different strains of Newcastle disease, infectious bursal disease and Marek's disease viruses.
A double construct vaccine of turkey herpesvirus (HVT) was prepared that contains the fusion (F) gene from Newcastle disease virus (NDV) and the viral protein 2 (VP2) gene from infectious bursal disease virus (IBDV). Safety of the vaccine (HVT-ND-IBD) was confirmed and efficacy was evaluated after subcutaneous (SC) vaccination at 1 day of age or the route of vaccination. Challenges were performed with velogenic NDV strains (Texas GB and Herts Weybridge 33/56), with different strains of IBDV (classical strain STC; very virulent strain CS89 and variant E strain) and with Marek's disease virus (MDV) strain RB1B. Vaccination with HVT-ND-IBD induced a high level of protection against these challenges. Vaccination with HVT is often combined with Rispens CVI988 vaccine and live ND vaccines for higher and earlier, MD and ND protection, respectively. HVT-ND-IBD vaccination in combination with these vaccines showed MD protection as early as 4 days post vaccination and ND protection as early as 2 weeks post vaccination. The long protection as seen with HVT vaccination was confirmed by demonstrating protection against NDV up to 60 weeks. Finally, to evaluate the performance of the vaccine in commercial birds with maternally-derived antibodies, two field trials were performed, using vaccination in broilers and SC vaccination in combination with Rispens CVI988 vaccine in layer-type birds. The efficacy was confirmed for all components by challenges. These results demonstrate that HVT-ND-IBD is a safe and highly efficacious vaccine for simultaneous control of ND, IBD and MD. A double construct HVT vaccine with the NDV F and the IBDV VP2 genes was prepared. The vaccine protects against three important diseases: MDV, NDV and IBDV. and sub-cutaneous vaccination was evaluated in the field in commercial chickens.
Topics: Animals; Birnaviridae Infections; Chickens; Female; Herpesvirus 2, Gallid; Infectious bursal disease virus; Male; Marek Disease; Newcastle Disease; Newcastle disease virus; Poultry Diseases; Specific Pathogen-Free Organisms; Vaccination; Vaccines, Attenuated; Viral Vaccines
PubMed: 33063529
DOI: 10.1080/03079457.2020.1828567 -
Viruses Dec 2022Marek's disease virus (MDV) infection results in Marek's disease (MD) in chickens, a lymphoproliferative and oncogenic deadly disease, leading to severe economic losses....
Marek's disease virus (MDV) infection results in Marek's disease (MD) in chickens, a lymphoproliferative and oncogenic deadly disease, leading to severe economic losses. The spleen and bursa are the most important lymphoid and major target organs for MDV replication. The immune response elicited by MDV replication in the spleen and bursa is critical for the formation of latent MDV infection and reactivation. However, the mechanism of the host immune response induced by MDV in these key lymphoid organs during the latent and reactivation infection phases is not well understood. In the study, we focused on the replication dynamics of a vaccine MDV strain MDV/CVI988 and a very virulent MDV strain MDV/RB1B in the spleen and bursa in the latent and reactivation infection phases (7-28 days post-inoculation [dpi]), as well as the expression of some previously characterized immune-related molecules. The results showed that the replication ability of MDV/RB1B was significantly stronger than that of MDV/CVI988 within 28 days post-infection, and the replication levels of both MDV strains in the spleen were significantly higher than those in the bursa. During the latent and reactivation phase of MDV infection (7-28 dpi), the transcriptional upregulation of chicken IL-1β, IL6, IL-8L1 IFN-γ and PML in the spleen and bursa induced by MDV/RB1B infection was overall stronger than that of MDV/CVI988. However, compared to MDV/RB1Binfection, MDV/CVI988 infection resulted in a more effective transcriptional activation of CCL4 in the latent infection phase (7-14 dpi), which may be a characteristic distinguishing MDV vaccine strain from the very virulent strain.
Topics: Animals; Cytokines; Spleen; Marek Disease; Chickens; Herpesvirus 2, Gallid; Marek Disease Vaccines; Latent Infection
PubMed: 36680047
DOI: 10.3390/v15010006