Industry-wide surveillance of Marek’s disease virus on commercial poultry farms

Kennedy, David; Cairns, Christopher; Jones, Matthew; Bell, Andrew S.; Salathé, Rahel; Baigent, Susan J.; Nair, Venugopal; Dunn, Patricia A.; Read, Andrew F.

doi:10.1101/075192

Cited by 9 publications

(17 citation statements)

References 37 publications

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“…The data used in this study are qPCR data reflecting the virus copy number (VCN) per mg of dust. These data were originally collected as part of a surveillance study quantifying the spatial and temporal variation of MDV across farms in Pennsylvania (Kennedy et al 2017). We use two representative datasets from that study: the data from Farm A House 1, and the data from Farm E House 4 (fig.…”

Section: Methodsmentioning

confidence: 99%

“…Points are the log mean plus one virus copy number per mg of dust collected at each sample time. Under the assumption that noise in the data is homoscedastic and normally distributed, bars show 95% confidence intervals around maximum likelihood estimates of virus copy number per mg of dust (Kennedy et al 2017). Note that in rare circumstances, the error bars do not overlap the data points because the log mean virus concentration differs slightly from the maximum likelihood virus concentration.…”

Section: Methodsmentioning

confidence: 99%

“…Yet the ecology of MDV is poorly understood. This is perhaps most clearly exemplified by the conventional wisdom saying that the virus is ubiquitously found on industrialized poultry farms (Office International des-Epizooties 2010; Dunn 2013), despite recent surveillance data suggesting that the virus may not be present on a large fraction of farms (Groves et al 2008; Wajid et al 2013; Walkden-Brown et al 2013; Bettridge et al 2014; Kennedy et al 2015b; Ralapanawe et al 2015; Kennedy et al 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Surveillance data have shown that the concentration of MDV in dust can vary several orders of magnitude between farms and within farms over time (Walkden-Brown et al 2013; Kennedy et al 2017). The underlying cause of this variation is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Modeling Marek’s disease virus transmission: a framework for evaluating the impact of farming practices and evolution on disease

Kennedy

Dunn

Read

2017

Preprint

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Marek's disease virus (MDV) is a pathogen of chickens whose control has twice been un-7 dermined by pathogen evolution. Disease ecology is believed to be the main driver of this 8 evolution, yet mathematical models of MDV disease ecology have never been confronted 9 with data to test their reliability. Here, we develop a suite of MDV models that differ in 10 the ecological mechanisms they include. We fit these models with maximum likelihood in 11'pomp' to data on MDV concentration in dust collected from two commercial broiler farms. 12Using AIC to compare the models, we find that virus dynamics are influenced by between-13 flock variation in host susceptibility to virus, shedding rate from infected birds, and cleanout 14 efficiency. We also find evidence that virus is reintroduced to farms approximately once per

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modeling Marek’s disease virus transmission: a framework for evaluating the impact of farming practices and evolution on disease

Kennedy

Dunn

Read

2017

Preprint

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“…A potential role of current vaccines at driving virulence due to their inability to prevent infection and spread has been demonstrated (5). As vaccinated birds are still susceptible to superinfection by more virulent MDV subtypes, co-infection with vaccine and pathogenic strains are common in clinical materials such as poultry house dust (8).…”

Section: Introductionmentioning

confidence: 99%

Pervasive differential splicing in Marek’s Disease Virus can discriminate CVI-988 vaccine strain from RB-1B virulent strain in chicken embryonic fibroblasts

Sadigh

Tahiri-Alaoui

Spatz

et al. 2019

Preprint

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Marek’s disease is a major scourge challenging poultry health worldwide. It is caused by the highly contagious Marek’s disease virus (MDV), an alphaherpesvirus. Here we show that, similar to other members of its Herpesviridae family, MDV also presents a complex landscape of splicing events, most of which are uncharacterised and/or not annotated. Quite strikingly, and although the biological relevance of this fact is unknown, we found that a number of viral splicing isoforms are strain-specific despite the close sequence similarity of the strains considered, virulent RB-1B and vaccine CVI-988. We validated our findings by devising an assay that discriminates infections caused by the two strains in chicken embryonic fibroblasts based on the presence of some RNA species. To our knowledge, this study is the first ever to accomplish such a result, emphasizing how important a comprehensive knowledge of the viral transcriptome can be to understand viral pathogenesis.ImportanceMarek’s disease virus (MDV) causes an agro-economically important disease of chickens worldwide. Although commercial poultry are vaccinated against MDV, it is not possible to achieve sterilising immunity, and available vaccines can only protect chickens against the symptoms of the disease. Vaccinated chicken often become superinfected with virulent strains, shedding virus into the environment. The most effective MDV vaccine strain, CVI-988, shares >99% sequence identity with the prototype virulent virus strain RB-1B. Interestingly, our work shows that despite their almost identical sequences MDV strains CVI-988 and RB-1B have significantly different splicing profiles, and hence transcriptomes. We independently validated this discovery by detecting with real-time PCR some splicing isoforms expressed by MDV strain CVI-988 and absent in the transcriptome of the RB-1B strain. These results indicate that the coding potential of MDV might be much larger than previously thought, and suggest a likely underestimation of the role of the viral transcriptome in the pathogenesis and prevention of MDV.

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Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance

Kennedy

Read

2018

Proc. Natl. Acad. Sci. U.S.A.

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Vaccines and antimicrobial drugs both impose strong selection for resistance. Yet only drug resistance is a major challenge for 21st century medicine. Why is drug resistance ubiquitous and not vaccine resistance? Part of the answer is that vaccine resistance is far less likely to evolve than drug resistance. But what happens when vaccine resistance does evolve? We review six putative cases. We find that in contrast to drug resistance, vaccine resistance is harder to detect and harder to confirm and that the mechanistic basis is less well understood. Nevertheless, in the cases we examined, the pronounced health benefits associated with vaccination have largely been sustained. Thus, we contend that vaccine resistance is less of a concern than drug resistance because it is less likely to evolve and when it does, it is less harmful to human and animal health and well-being. Studies of pathogen strains that evolve the capacity to replicate and transmit from vaccinated hosts will enhance our ability to develop next-generation vaccines that minimize the risk of harmful pathogen evolution.

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Industry-wide surveillance of Marek’s disease virus on commercial poultry farms

Abstract: Marek's disease (MD) is a lymphomatous and neuropathic disease of domestic fowl caused by an alphaherpesvirus, designated Marek's disease virus (MDV), belonging to the genus

Cited by 9 publications

References 37 publications

Modeling Marek’s disease virus transmission: a framework for evaluating the impact of farming practices and evolution on disease

Modeling Marek’s disease virus transmission: a framework for evaluating the impact of farming practices and evolution on disease

Pervasive differential splicing in Marek’s Disease Virus can discriminate CVI-988 vaccine strain from RB-1B virulent strain in chicken embryonic fibroblasts

Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance

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