In vivo characterisation of two Australian isolates of Marek's disease virus including pathology, viral load and neuropathotyping based on clinical signs

2015 ◽  
Vol 93 (7) ◽  
pp. 240-247 ◽  
Author(s):  
SJ Wajid ◽  
SW Walkden-Brown ◽  
BA Vanselow ◽  
AFMF Islam ◽  
KG Renz
Keyword(s):  
Viral Load ◽  
Disease Virus ◽  
Clinical Signs ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease

scholarly journals The Tegument Protein pUL47 of Marek’s Disease Virus Is Necessary for Horizontal Transmission and Is Important for Expression of Glycoprotein gC

2020 ◽  
Vol 95 (2) ◽  
pp. e01645-20
Author(s):  
Aurélien Chuard ◽  
Katia Courvoisier-Guyader ◽  
Sylvie Rémy ◽  
Stephen Spatz ◽  
Caroline Denesvre ◽  
...  
Keyword(s):  
Disease Virus ◽  
Horizontal Transmission ◽  
Marek's Disease Virus ◽  
Viral Transmission ◽  
Natural Host ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease

ABSTRACTViral tropism and transmission of herpesviruses are best studied in their natural host for maximal biological relevance. In the case of alphaherpesviruses, few reports have focused on those aspects, primarily because of the few animal models available as natural hosts that are compatible with such studies. Here, using Marek’s disease virus (MDV), a highly contagious and deadly alphaherpesvirus of chickens, we analyze the role of tegument proteins pUL47 and pUL48 in the whole life cycle of the virus. We report that a virus lacking the UL48 gene (vΔUL48) is impaired in growth in cell culture and has diminished virulence in vivo. In contrast, a virus lacking UL47 (vΔUL47) is unaffected in its growth in vitro and is as virulent in vivo as the wild-type (WT) virus. Surprisingly, we observed that vΔUL47 was unable to be horizontally transmitted to naive chickens, in contrast to the WT virus. In addition, we show that pUL47 is important for the splicing of UL44 transcripts encoding glycoprotein gC, a protein known as being essential for horizontal transmission of MDV. Importantly, we observed that the levels of gC are lower in the absence of pUL47. Notably, this phenotype is similar to that of another transmission-incompetent mutant ΔUL54, which also affects the splicing of UL44 transcripts. This is the first study describing the role of pUL47 in both viral transmission and the splicing and expression of gC.IMPORTANCE Host-to-host transmission of viruses is ideally studied in vivo in the natural host. Veterinary viruses such as Marek’s disease virus (MDV) are, therefore, models of choice to explore these aspects. The natural host of MDV, the chicken, is small, inexpensive, and economically important. MDV is a deadly and contagious herpesvirus that can kill infected animals in less than 4 weeks. The virus naturally infects epithelial cells of the feather follicle epithelium from where it is shed into the environment. In this study, we demonstrate that the viral protein pUL47 is an essential factor for bird-to-bird transmission of the virus. We provide some molecular basis to this function by showing that pUL47 enhances the splicing and the expression of another viral gene, UL44, which is essential for viral transmission. pUL47 may have a similar function in human herpesviruses such as varicella-zoster virus or herpes simplex viruses.

scholarly journals The RNA Subunit of Telomerase Is Encoded by Marek's Disease Virus

2003 ◽  
Vol 77 (10) ◽  
pp. 5985-5996 ◽  
Author(s):  
Laëtitia Fragnet ◽  
Maria A. Blasco ◽  
Wolfram Klapper ◽  
Denis Rasschaert
Keyword(s):  
Cell Line ◽  
Disease Virus ◽  
Telomerase Activity ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Blood Leukocytes ◽  
Potential Implication

ABSTRACT Marek's disease virus (MDV) is a herpesvirus of chickens that induces T lymphomas and tumors within 4 to 5 weeks of infection. Although the ability of MDV to induce tumors was demonstrated many years ago and although a number of viral oncogenic proteins have been identified, the mechanism by which the MDV is implicated in tumorigenesis is still unknown. We report the identification of a virus-encoded RNA telomerase subunit (vTR) within the genome of MDV. This gene is found in the genomic DNA of the oncogenic MDV strains, whereas it is not carried by the nononcogenic MDV strains. The vTR sequence exhibits 88% sequence identity with the chicken gene (cTR). Our functional analysis suggests that this telomerase RNA can reconstitute telomerase activity in a heterologous system (the knockout murine TR−/− cell line) by interacting with the telomerase protein component encoded by the host cell. We have also demonstrated that the vTR promoter region is efficient whatever the species of cell line considered and that vTR is expressed in vivo in peripheral blood leukocytes from chickens infected with the oncogenic MDV-RB1B and the vaccine MDV-Rispens strains. The functionality of the vTR gene and the potential implication of vTR in the oncogenesis induced by MDV is discussed.

scholarly journals Marek’s Disease Virus Cluster 3 miRNAs Restrict Virus’ Early Cytolytic Replication and Pathogenesis

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1317
Author(s):  
Yifei Liao ◽  
Guoqing Zhuang ◽  
Aijun Sun ◽  
Owais A. Khan ◽  
Blanca Lupiani ◽  
...  
Keyword(s):  
Disease Virus ◽  
Mature Mirnas ◽  
Peripheral Blood Lymphocytes ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Virus Reactivation ◽  
Death Time

Herpesvirus-encoded microRNAs (miRNAs) have been discovered in infected cells; however, lack of a suitable animal model has hampered functional analyses of viral miRNAs in vivo. Marek’s disease virus (MDV) (Gallid alphaherpesvirus 2, GaHV-2) genome contains 14 miRNA precursors, which encode 26 mature miRNAs, grouped into three clusters. In this study, the role of MDV-encoded cluster 3 miRNAs, also known as mdv1-miR-M8-M10, in pathogenesis was evaluated in chickens, the natural host of MDV. Our results show that deletion of cluster 3 miRNAs did not affect virus replication and plaque size in cell culture, but increased early cytolytic replication of MDV in chickens. We also observed that deletion of cluster 3 miRNAs resulted in significantly higher virus reactivation from peripheral blood lymphocytes. In addition, pathogenesis studies showed that deletion of cluster 3 miRNAs resulted in more severe atrophy of lymphoid organs and reduced mean death time, but did not affect the incidence of MDV-associated visceral tumors. We confirmed these results by generating a cluster 3 miRNA revertant virus in which the parental MDV phenotype was restored. To the best of our knowledge, our study provides the first evidence that MDV cluster 3 miRNAs play an important role in modulating MDV pathogenesis.

scholarly journals Macrophages from Susceptible and Resistant Chicken Lines have Different Transcriptomes following Marek’s Disease Virus Infection

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 74 ◽  
Author(s):  
Pankaj Chakraborty ◽  
Richard Kuo ◽  
Lonneke Vervelde ◽  
Bernadette M. Dutia ◽  
Pete Kaiser ◽  
...  
Keyword(s):  
Disease Virus ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Activated T Cells ◽  
Defense Strategies ◽  
Infection Resistance

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.

scholarly journals Safety and Efficacy Evaluation of Recombinant Marek’s Disease Virus with REV-LTR

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 399 ◽  
Author(s):  
Cuiping Song ◽  
Yang Yang ◽  
Jing Hu ◽  
Shengqing Yu ◽  
Yingjie Sun ◽  
...  
Keyword(s):  
Disease Virus ◽  
Clinical Signs ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Efficacy Evaluation ◽  
Live Attenuated Vaccine ◽  
Safety And Efficacy

Recently, chickens vaccinated with the CVI988/Rispens vaccine showed increased tumor incidence. Moreover, many strains of Marek’s disease virus (MDV) that were naturally integrated with the long terminal repeat (LTR) of the avian reticuloendotheliosis virus (REV) have been isolated, which means it is necessary to develop a new vaccine. In this study, two LTR sequences were inserted into Rispens to construct a recombinant MDV (rMDV). Then, the safety and efficacy of rMDV were evaluated separately in chickens. The growth rate curves showed that the insertion of REV-LTR into MDV enabled a faster replication in vitro than Rispens. Chickens immunized with high or repeated dose rMDV had no MD clinical signs. Further, no tumor, tissue lesions, or evident pathological changes were observed in the chicken organs. Polymerase chain reaction (PCR) and virus isolation revealed that rMDV had the ability to spread horizontally to non-immunized chickens and had no impact on the environment. After five passages in chickens, there were no obvious lesions, and the LTR insertion was stable. There were also no deletions or mutations, which indicates that rMDV is safe in chickens. In addition, rMDV has an advantage over Rispens against vvMDV Md5 at low doses. All results demonstrate that the transgenic strain of rMDV with REV-LTR can be used as a live attenuated vaccine candidate.

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