Efficacy and safety of cell associated vaccines against Marek's disease virus grown in a continuous cell line from chickens

Geerligs, H.J.; Quanz, Sandra; Suurland, Brenda; Spijkers, Ine; Rodenberg, Jeff; Davelaar, F. G.; Jongsma, Berend; Kumar, Mahesh

doi:10.1016/j.vaccine.2008.07.080

Cited by 14 publications

(11 citation statements)

References 8 publications

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“…In our studies though, the viral titres obtained in ESCDL-1 are in the range of those described for SogE-QM7 cells [14]. Also, as described earlier for the QM7 derived line [14], ESCDL-1 were fully susceptible to all GaHV-2 tested, which did induce a cytopathic effect at their first passage, unlike in JBJ-1 cells [15]. In addition to the evaluation of viral susceptibility, we show here evidence for a permissiveness that is unaffected by the number of serial passages, a feature of major interest for virology studies.…”

Section: Discussionsupporting

confidence: 81%

“…A limited number of permanent cell-lines supporting GaHV-2 replication have been described, some being less permissive than primary cells [10, 11], and some even contaminated by MDV [12, 13]. Interestingly, SOgE cells, derived from QM7 cell-line expressing GaHV-2 glycoprotein E, were described to support the replication of virulent, as well as cell-adapted vaccine viruses [14], and another cell-line, JBJ-1 is currently under study for vaccine production with cell-adapted vaccine Mardiviruses [15]. As experiments designed to generate new cell lines from primary cells [10], some combined with chemical treatment [10, 11], yielded disappointing results regarding the overall susceptibility of these cells for Mardiviruses, we hypothesized that a rationale for building a better cell-line could be based on the use of embryonic stem (ES) cells.…”

Section: Introductionmentioning

confidence: 99%

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ESCDL-1, a new cell line derived from chicken embryonic stem cells, supports efficient replication of Mardiviruses

et al. 2017

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Marek’s disease virus is the etiological agent of a major lymphoproliferative disorder in poultry and the prototype of the Mardivirus genus. Primary avian somatic cells are currently used for virus replication and vaccine production, but they are largely refractory to any genetic modification compatible with the preservation of intact viral susceptibility. We explored the concept of induction of viral replication permissiveness in an established pluripotent chicken embryonic stem cell-line (cES) in order to derive a new fully susceptible cell-line. Chicken ES cells were not permissive for Mardivirus infection, but as soon as differentiation was triggered, replication of Marek’s disease virus was detected. From a panel of cyto-differentiating agents, hexamethylene bis (acetamide) (HMBA) was found to be the most efficient regarding the induction of permissiveness. These initial findings prompted us to analyse the effect of HMBA on gene expression, to derive a new mesenchymal cell line, the so-called ESCDL-1, and monitor its susceptibility for Mardivirus replication. All Mardiviruses tested so far replicated equally well on primary embryonic skin cells and on ESCDL-1, and the latter showed no variation related to its passage number in its permissiveness for virus infection. Viral morphogenesis studies confirmed efficient multiplication with, as in other in vitro models, no extra-cellular virus production. We could show that ESCDL-1 can be transfected to express a transgene and subsequently cloned without any loss in permissiveness. Consequently, ESCDL-1 was genetically modified to complement viral gene deletions thus yielding stable trans-complementing cell lines. We herein claim that derivation of stable differentiated cell-lines from cES cell lines might be an alternative solution to the cultivation of primary cells for virology studies.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

ESCDL-1, a new cell line derived from chicken embryonic stem cells, supports efficient replication of Mardiviruses

et al. 2017

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“…AF147806) and HVT strain FC126 (GenBank no. AF291866) were propagated in CEFs or DF-1 cells and titrated as described previously (69). Commercially available antibodies were used, including rabbit anti-HA, mouse anti-Flag, and mouse antiactin (Sigma-Aldrich, St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Marek’s Disease Virus RLORF4 Inhibits Type I Interferon Production by Antagonizing NF-κB Activation

Liu

Gao

et al. 2019

J Virol

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Marek’s disease virus (MDV), which causes T cell lymphomas in chickens, is economically important and has contributed to knowledge of herpesvirus-associated oncogenicity. The DNA-sensing pathway induces innate immune responses against DNA virus infection, and nuclear factor κB (NF-κB) signaling is critical for the establishment of innate immunity. Here, we report that RLORF4, an MDV-specific protein directly involved in viral attenuation, is an inhibitor of the DNA-sensing pathway. The results showed that ectopically expressed RLORF4 blocked beta interferon (IFN-β) promoter activation induced by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). RLORF4 selectively inhibited the activation of NF-κB but not IFN-regulatory factor 7. RLORF4 was found to bind the endogenous NF-κB subunits p65 and p50, and it also bound to the Rel homology domains of these subunits. Furthermore, RLORF4 suppressed the nuclear translocation of p65 and p50 mediated by tumor necrosis factor alpha and interferon-stimulatory DNA. Finally, deletion of RLORF4 from the MDV genome promoted IFN-β and interleukin-6 (IL-6) production in vitro and in vivo. In the absence of RLORF4, the host cellular immunity was significantly increased, and reduced viral titers were observed during infection of chickens. Our results suggest that the RLORF4-mediated suppression of the host antiviral innate immunity might play an important role in MDV pathogenesis. IMPORTANCE Marek’s disease virus (MDV) RLORF4 has been shown to be directly involved in the attenuation of MDV upon serial passages in vitro; however, the exact function of this protein during viral infection was not well characterized. This study demonstrated that RLORF4 significantly inhibits cGAS-STING-mediated NF-κB activation by binding to the Rel homology domains of the NF-κB subunits p65 and p50, interrupting their translocation to the nuclei and thereby inhibiting IFN-β production. Furthermore, RLORF4 deficiency promoted the induction of IFN-β and downstream IFN-stimulated genes during MDV infection in chickens. Our results suggest that the contribution of RLORF4 to MDV virulence may stem from its inhibition of viral DNA-triggered IFN-β responses.

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“…The chickens that died after challenge and those that were sacrificed at the end of the challenge period were subjected to gross and histopathological observations for MD lesions in the liver, kidneys, spleen, nerves, and skin [17]. The protection index (PI) was calculated by the following formula [38]:…”

Section: Methodsmentioning

confidence: 99%

Protection conferred by a recombinant Marek’s disease virus that expresses the spike protein from infectious bronchitis virus in specific pathogen-free chicken

Zhang

YeZhen

et al. 2012

Virol J

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BackgroundIn many countries, the predominant field isolates of infectious bronchitis virus (IBV) have been classified as QX-like strains since 1996. However, no commercial vaccines that are specific for this type of IBV are currently available. Therefore, there is an urgent need to develop novel vaccines that prevent QX-like IBV infection.ResultsA recombinant Marek’s disease virus (MDV), rMDV-S1, that expresses the S1 subunit of the spike (S) protein from the QX-like infectious bronchitis virus (IBV) was constructed by inserting the IBV S1 gene into the genome of the CVI988/Rispens strain of MDV. Specific pathogen-free (SPF) chickens that were vaccinated with rMDV-S1 were protected when challenged with the QX-like IBV. They were observed to have mild clinical signs of disease, a short virus-shedding period and low mortality. Additionally, the rMDV-S1 conferred full protection to chickens against virulent MDV, as did the CVI988/Rispens strain.ConclusionsOur results demonstrate that rMDV-S1 is an effective and promising recombinant vaccine for the prevention of QX-like IBV infection.

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Efficacy and safety of cell associated vaccines against Marek's disease virus grown in a continuous cell line from chickens

Cited by 14 publications

References 8 publications

ESCDL-1, a new cell line derived from chicken embryonic stem cells, supports efficient replication of Mardiviruses

ESCDL-1, a new cell line derived from chicken embryonic stem cells, supports efficient replication of Mardiviruses

Marek’s Disease Virus RLORF4 Inhibits Type I Interferon Production by Antagonizing NF-κB Activation

Protection conferred by a recombinant Marek’s disease virus that expresses the spike protein from infectious bronchitis virus in specific pathogen-free chicken

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