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PLoS Biology Mar 2020Many livestock and human vaccines are leaky because they block symptoms but do not prevent infection or onward transmission. This leakiness is concerning because it...
Many livestock and human vaccines are leaky because they block symptoms but do not prevent infection or onward transmission. This leakiness is concerning because it increases vaccination coverage required to prevent disease spread and can promote evolution of increased pathogen virulence. Despite leakiness, vaccination may reduce pathogen load, affecting disease transmission dynamics. However, the impacts on post-transmission disease development and infectiousness in contact individuals are unknown. Here, we use transmission experiments involving Marek disease virus (MDV) in chickens to show that vaccination with a leaky vaccine substantially reduces viral load in both vaccinated individuals and unvaccinated contact individuals they infect. Consequently, contact birds are less likely to develop disease symptoms or die, show less severe symptoms, and shed less infectious virus themselves, when infected by vaccinated birds. These results highlight that even partial vaccination with a leaky vaccine can have unforeseen positive consequences in controlling the spread and symptoms of disease.
Topics: Animals; Chickens; Feathers; Herpesvirus 2, Gallid; Host-Pathogen Interactions; Marek Disease; Vaccination; Viral Load; Viral Vaccines; Virulence; Virus Shedding
PubMed: 32134914
DOI: 10.1371/journal.pbio.3000619 -
Journal of Comparative Pathology Jul 2022Marek's disease (MD) is caused by virulent strains of Gallid alphaherpesvirus type 2 (MD virus serotype 1; MDV 1) and frequently causes a lymphoproliferative disorder in...
Marek's disease (MD) is caused by virulent strains of Gallid alphaherpesvirus type 2 (MD virus serotype 1; MDV 1) and frequently causes a lymphoproliferative disorder in poultry and other galliform birds worldwide. However, within the peafowl (Phasianinae) subfamily, there are only rare confirmed reports of MD. Here we report MD in an Indian peafowl (Pavo cristatus), which clinically presented with hindlimb paraparesis and intraocular swelling of the right eye. Soft, off-white to tan masses within the right eye, sciatic nerves and coelomic cavity were identified at post-mortem examination which effaced the cranial pole of the kidneys and diffusely effaced the testes. Lymphoid neoplasia was identified histologically at all of these sites and there was extensive hepatic lymphoid cell infiltration, which had not been grossly evident. The T-cell origin of the lymphoid cells was confirmed by immunohistochemistry for CD3 antigen. A virulent strain of MDV 1 was detected by real-time polymerase chain reaction in DNA samples extracted from the kidney and testes. As MD is rare in peafowl it should be considered as a differential diagnosis for intraocular and coelomic masses with associated clinical signs.
Topics: Animals; Chickens; Eye Diseases; Herpesvirus 2, Gallid; Marek Disease; Paraparesis; Poultry Diseases
PubMed: 35817540
DOI: 10.1016/j.jcpa.2022.04.003 -
Journal of Virology Mar 2022Latency is a hallmark of herpesviruses, allowing them to persist in their host without virion production. Acute exposure to hypoxia (below 3% O) was identified as a...
Latency is a hallmark of herpesviruses, allowing them to persist in their host without virion production. Acute exposure to hypoxia (below 3% O) was identified as a trigger of latent-to-lytic switch (reactivation) for human oncogenic gammaherpesviruses (Kaposi's sarcoma-associated virus [KSHV] and Epstein-Barr virus [EBV]). Therefore, we hypothesized that hypoxia could also induce reactivation of Marek's disease virus (MDV), which shares biological properties with EBV and KSHV (notably oncogenic properties), in lymphocytes. Acute exposure to hypoxia (1% O) of two MDV-latently infected cell lines derived from MD tumors (3867K and MSB-1) induced MDV reactivation. A bioinformatic analysis of the RB-1B MDV genome revealed 214 putative hypoxia response element consensus sequences on 119 open reading frames. Reverse transcriptase quantitative PCR (RT-qPCR) analysis showed five MDV genes strongly upregulated early after hypoxia. In 3867K cells under normoxia, pharmacological agents mimicking hypoxia (MLN4924 and CoCl) increased MDV reactivation, but to a lower level than real hypoxia. Overexpression of wild-type or stabilized human hypoxia inducible factor 1α (HIF-1α) in MSB-1 cells in normoxia also promoted MDV reactivation. Under such conditions, the lytic cycle was detected in cells with a sustainable HIF-1α expression but also in HIF-1α-negative cells, indicating that MDV reactivation is mediated by HIF-1 in a direct and/or indirect manner. Lastly, we demonstrated by a reporter assay that HIF-1α overexpression induced the transactivation of two viral promoters, shown to be upregulated in hypoxia. These results suggest that hypoxia may play a crucial role in the late lytic replication phase observed in MDV-infected chickens exhibiting tumors, since a hypoxic microenvironment is a hallmark of most solid tumors. Latent-to-lytic switch of herpesviruses (also known as reactivation) is responsible for pathology recurrences and/or viral shedding. Studying physiological triggers of reactivation is therefore important for health to limit lesions and viral transmission. Marek's disease virus (MDV) is a potent oncogenic alphaherpesvirus establishing latency in T lymphocytes and causing lethal T lymphomas in chickens. , a second lytic phase is observed during the tumoral stage. Hypoxia being a hallmark of tumors, we wondered whether hypoxia induces MDV reactivation in latently infected T lymphocytes, like previously shown for EBV and KSHV in B lymphocytes. In this study, we demonstrated that acute hypoxia (1% O) triggers MDV reactivation in two MDV transformed T-cell lines. We provide some molecular basis of this reactivation by showing that hypoxia inducible factor 1 (HIF-1) overexpression induces MDV reactivation to an extent similar to that of hypoxia after 24 h. Hypoxia is therefore a reactivation stimulus shared by mammalian and avian oncogenic herpesviruses of different genera.
Topics: Animals; Cell Line, Tumor; Chickens; Herpesvirus 2, Gallid; Hypoxia; Hypoxia-Inducible Factor 1; Lymphoma; Marek Disease; T-Lymphocytes; Virus Activation
PubMed: 34936483
DOI: 10.1128/JVI.01427-21 -
Poultry Science Dec 2020The aim of this study was to determine the effect of vaccinations for avian infectious bronchitis with Newcastle disease (IB/ND) and Marek's disease (MD) on the...
Effects of avian infectious bronchitis with Newcastle disease and Marek's disease vaccinations on the expression of toll-like receptors and avian β-defensins in the kidneys of broiler chicks.
The aim of this study was to determine the effect of vaccinations for avian infectious bronchitis with Newcastle disease (IB/ND) and Marek's disease (MD) on the expression of toll-like receptors (TLR) that recognize viral RNA and microbial DNA, and AvBD in chick kidneys. Day-old chicks were vaccinated with MD or IB/ND vaccines or received no treatment (control group). The gene expression of TLR and AvBD in the kidneys of 3-day-old chicks and 10-day-old chicks was examined using real-time PCR. The localization of AvBD2 and AvBD4 was examined by immunohistochemistry at day three only. At 3 days of age, the expression of TLR7 and TLR21 was significantly higher in the IB/ND group (but not in the MD group) than in the control group. Conversely, at 10 days of age there was no significant difference in the expression of the three TLR between groups. In the 3-day-old chicks the expression levels of AvBD4, 5, 6, and 7 were higher in the MD group than in the control group. Furthermore, at this age, the expression levels of other AvBD were not significantly different between the control and vaccination (MD and IB/ND) groups. At 10 days of age, no AvBD expression was affected by MD and IB/ND vaccinations. Immunohistochemistry results localized AvBD2 in the leukocytes in the interstitial tissue and AvBD4 in the surface of microvillus epithelial cells of renal tubules, and in the epithelial cells of the collecting ducts and ureter. The localization of AvBD2 and AvBD4 was identified in all chicks. We suggest that the expression of innate immune molecules (including TLR and AvBD) in kidneys could be modulated by MD and IB/ND vaccination when performed at the day-old stage. Although the effects of both vaccinations may subside within 10 days, the enhanced expression of those innate immune molecules may support the innate immunodefense function in the kidneys of young chicks.
Topics: Animals; Bronchitis; Chickens; Gene Expression Regulation; Kidney; Marek Disease; Newcastle Disease; Poultry Diseases; Toll-Like Receptors; Vaccination; Viral Vaccines; beta-Defensins
PubMed: 33248626
DOI: 10.1016/j.psj.2020.08.071 -
Avian Diseases Oct 2022Marek's disease (MD) is a highly contagious, lymphoproliferative poultry disease caused by the oncogenic herpesvirus, serotype 1 Marek's disease virus (MDV-1), or 2...
Marek's disease (MD) is a highly contagious, lymphoproliferative poultry disease caused by the oncogenic herpesvirus, serotype 1 Marek's disease virus (MDV-1), or 2 (GaHV-2). MDV strains have shown a continued evolution of virulence leading to immune failure, and MD cases continue to occur or surge. , the major MDV-1 oncoprotein, induces T-cell neoplastic transformation through several mechanisms including inhibition of apoptosis, cell cycle regulation, and serum-anchorage independent growth. There is no current information on the MDV serotypes and pathotypes circulating in vaccinated commercial farms in Iran, where the birds are vaccinated at the hatchery with GaHV-2 and 1 (MeHV-1) vaccines. This study reports the molecular characterization of a GaHV-2 strain detected in 19 flocks of Iranian layer farms exhibiting MDV-1-like clinical signs and visceral lymphomas. Based on sequencing and phylogenetic analysis of the gene, the Iranian GaHV-2 isolates could be divided into two separate clades regarding molecular features. The clade containing strains was closely related to Italian, Indian, and Hungarian virulent isolates, and the clade was related to American very virulent plus (vv+) isolates. For the first time, the MDV-1 virus was characterized by an outbreak in poultry flocks in Iran. Although MDV-1 strains obtained in Iran's present outbreak are presumably related to virulent (v) and vv+ pathotypes based on nucleotide, amino acid, and phylogenetic analysis of the viruses, they are not confirmed so far. Thus, it is highly recommended to perform further analyses to demonstrate the pathotype characteristics .
Topics: Amino Acids; Animals; Chickens; Herpesvirus 2, Gallid; Iran; Marek Disease; Nucleotides; Oncogene Proteins; Phylogeny; Poultry; Poultry Diseases
PubMed: 36106908
DOI: 10.1637/aviandiseases-D-22-00018 -
Acta Virologica 2021Marek's disease (MD) is a lymphoproliferative disease of chickens with strong economic impact on poultry industry. Although successful vaccination has enabled control of... (Review)
Review
Marek's disease (MD) is a lymphoproliferative disease of chickens with strong economic impact on poultry industry. Although successful vaccination has enabled control of the disease, outbreaks occur in commercial flocks, resulting in substantial economic losses. Together with vaccination, accurate and fast diagnosis of MD remain the most important tools for its efficient control. MD diagnosis currently relies mainly on the identification of its causative agent, Marek's disease virus type 1 (MDV-1). Nucleic acid amplification techniques have been successfully applied for identification of MDV DNA in field samples and also for studies of virus-host interactions. In this review we want to summarize recent advances in the development of standard and quantitative PCR techniques and their use in rapid MD diagnosis, including differentiation of pathogenic and vaccine MD viruses. PCR protocols have served as a useful tool for clarification of processes associated with MDV infection in chickens, such as virus spread and release, and effect of vaccine virus on progress of MD. Here, we also describe a novel multi-species qPCR methodology for identification and quantification of MDV DNA, enabling its detection in various bird species that are the most susceptible to MDV infection. Keywords: Marek's disease; MDV; diagnosis; nucleic acid detection; duplex quantitative PCR.
Topics: Animals; Chickens; Herpesvirus 2, Gallid; Marek Disease; Nucleic Acid Amplification Techniques; Nucleic Acids; Poultry Diseases
PubMed: 33827220
DOI: 10.4149/av_2021_108 -
Viruses Jun 2017Marek's disease virus (MDV) and reticuloendotheliosis virus (REV) cause Marek's disease (MD) and reticuloendotheliosis (RE), respectively. Co-infection with MDV and REV...
Marek's disease virus (MDV) and reticuloendotheliosis virus (REV) cause Marek's disease (MD) and reticuloendotheliosis (RE), respectively. Co-infection with MDV and REV is common in chickens, causing serious losses to the poultry industry. However, experimental studies of such co-infection are lacking. In this study, Chinese field strains of MDV (ZW/15) and REV (JLR1501) were used as challenge viruses to evaluate the pathogenicity of co-infection and the influence of MD vaccination in chickens. Compared to the MDV-challenged group, the mortality and tumor rates increased significantly by 20.0% (76.7 to 96.7%) and 26.7% (53.3 to 80.0%), in the co-challenged group, respectively. The protective index of the MD vaccines CVI988 and 814 decreased by 33.3 (80.0 to 47.7) and 13.3 (90.0 to 76.7), respectively. These results indicated that MDV and REV co-infection significantly increased disease severity and reduced the vaccine efficacy. The MDV genome load showed no difference in the feather pulps and spleen, and pathogenicity-related MDV gene expression (, , , and ) in the spleen significantly increased at some time points in the co-challenged group. Clearly, synergistic pathogenicity occurred between MDV and REV, and the protective efficacy of existing MD vaccines was attenuated by co-infection with Chinese field MDV and REV strains.
Topics: Animals; Chickens; Coinfection; Herpesvirus 2, Gallid; Marek Disease; Marek Disease Vaccines; Poultry Diseases; Reticuloendotheliosis Viruses, Avian; Retroviridae Infections; Survival Analysis; Tumor Virus Infections; Viral Load
PubMed: 28635675
DOI: 10.3390/v9060158 -
Journal of Virology Dec 2023Marek's disease virus (MDV) is a highly infectious and oncogenic virus that can induce severe T cell lymphomas in chickens. MDV encodes more than 100 genes, most of...
Marek's disease virus (MDV) is a highly infectious and oncogenic virus that can induce severe T cell lymphomas in chickens. MDV encodes more than 100 genes, most of which have unknown functions. This work indicated that the gene is necessary for MDV early cytolytic replication in B lymphocytes. In addition, we have found that the deletion mutant has a comparative immunological protective effect with CVI988/Rispens vaccine strain against very virulent MDV challenge. This is a significant discovery that LORF9 can be exploited as a possible target for the development of an MDV gene deletion vaccine.
Topics: Animals; B-Lymphocytes; Chickens; Gene Deletion; Herpesvirus 2, Gallid; Marek Disease; Marek Disease Vaccines; Poultry Diseases; Virus Replication
PubMed: 38014947
DOI: 10.1128/jvi.01574-23 -
PLoS Pathogens Feb 2021Marek's disease virus (MDV) is a potent oncogenic alphaherpesvirus that elicits a rapid onset of malignant T-cell lymphomas in chickens. Three MDV types, including...
Marek's disease virus (MDV) is a potent oncogenic alphaherpesvirus that elicits a rapid onset of malignant T-cell lymphomas in chickens. Three MDV types, including GaHV-2 (MDV-1), GaHV-3 (MDV-2) and MeHV-1 (HVT), have been identified and all encode a US3 protein kinase. MDV-1 US3 is important for efficient virus growth in vitro. To study the role of US3 in MDV replication and pathogenicity, we generated an MDV-1 US3-null virus and chimeric viruses by replacing MDV-1 US3 with MDV-2 or HVT US3. Using MD as a natural virus-host model, we showed that both MDV-2 and HVT US3 partially rescued the growth deficiency of MDV-1 US3-null virus. In addition, deletion of MDV-1 US3 attenuated the virus resulting in higher survival rate and lower MDV specific tumor incidence, which could be partially compensated by MDV-2 and HVT US3. We also identified chicken histone deacetylase 1 (chHDAC1) as a common US3 substrate for all three MDV types while only US3 of MDV-1 and MDV-2 phosphorylate chHDAC2. We further determined that US3 of MDV-1 and HVT phosphorylate chHDAC1 at serine 406 (S406), while MDV-2 US3 phosphorylates S406, S410, and S415. In addition, MDV-1 US3 phosphorylates chHDAC2 at S407, while MDV-2 US3 targets S407 and S411. Furthermore, biochemical studies show that MDV US3 mediated phosphorylation of chHDAC1 and 2 affect their stability, transcriptional regulation activity, and interaction network. Using a class I HDAC specific inhibitor, we showed that MDV US3 mediated phosphorylation of chHDAC1 and 2 is involved in regulation of virus replication. Overall, we identified novel substrates for MDV US3 and characterized the role of MDV US3 in MDV pathogenesis.
Topics: Animals; Chickens; Herpesvirus 2, Gallid; Histone Deacetylase 1; Histone Deacetylase 2; Marek Disease; Protein Serine-Threonine Kinases; Viral Proteins; Virus Replication
PubMed: 33596269
DOI: 10.1371/journal.ppat.1009307 -
Microorganisms Jun 2021Herpesviruses are a group of double-strand DNA viruses that infect a wide range of hosts, including humans and animals. In the past decades, numerous methods have been... (Review)
Review
Herpesviruses are a group of double-strand DNA viruses that infect a wide range of hosts, including humans and animals. In the past decades, numerous methods have been developed to manipulate herpesviruses genomes, from the introduction of random mutations to specific genome editing. The development of genome manipulation methods has largely advanced the study of viral genes function, contributing not only to the understanding of herpesvirus biology and pathogenesis, but also the generation of novel vaccines and therapies to control and treat diseases. In this review, we summarize the major methods of herpesvirus genome manipulation with emphasis in their application to Marek's disease virus research.
PubMed: 34200544
DOI: 10.3390/microorganisms9061260