Sylvie l Benestad

• Norwegian Veterinary Institute

Background Classical scrapie in sheep is caused by several different strains rather than a single strain, as is the case for epidemic classical bovine spongiform encephalopathy (BSE). Polymorphisms R171 and K176 located in the β2-α2 loop region of sheep-PrP have been associated with potential protection for the propagation of classical scrapie. Me...

Aquaculture farming discharges large volumes of fish sludge, consisting of particulate organic matter from feed spill and feces. Fish sludge from land‐based salmonid aquaculture systems can potentially be used to feed low‐trophic species such as marine polychaetes and insects. Further use of these invertebrates as feed may provide a more sustainabl...

Chronic wasting disease (CWD) is an emerging disease in Europe. We report an increase in interspecies transmission capacity and zoonotic potential of a moose CWD isolate from Europe after passage in an ovine prion protein-expressing host. Those results indicated some CWD prions could acquire enhanced zoonotic properties following adaptation in an i...

Chronic wasting disease (CWD), a prion disease affecting cervids, has been known in North America (NA) since the 1960s and emerged in Norway in 2016. Surveillance and studies have revealed that there are different forms of CWD in Fennoscandia: contagious CWD in Norwegian reindeer and sporadic CWD in moose and red deer. Experimental studies have dem...

Chronic wasting disease (CWD) is a prion disease affecting deer, elk and moose in North America and reindeer, moose and red deer in Northern Europe. Pathogenesis is driven by the accumulation of PrPSc, a pathological form of the host’s cellular prion protein (PrPC), in the brain. CWD is contagious among North American cervids and Norwegian reindeer...

Finding alternative protein and lipid sources for aquafeeds is crucial for the sustainable growth of fed aquaculture. Upcycling industrial side streams and byproducts using extractive species can reduce waste and help reduce the sector's dependence on fish meal and fish oils. Polychaete worms (Hediste diversicolor) and black soldier fly (Hermetia i...

While animal prion diseases are a threat to human health, their zoonotic potential is generally inefficient because of interspecies prion transmission barriers. New animal models are required to provide an understanding of these prion transmission barriers and to assess the zoonotic potential of animal prion diseases. To address this goal, we gener...

The first case of CWD in a Norwegian red deer was detected by a routine ELISA test and confirmed by western blotting and immunohistochemistry in the brain stem of the animal. Two different western blotting tests were conducted independently in two different laboratories, showing that the red deer glycoprofile was different from the Norwegian CWD re...

Transmissible spongiform encephalopathies or prion diseases comprise diseases with different levels of contagiousness under natural conditions. The hypothesis has been raised that the chronic wasting disease (CWD) cases detected in Nordic moose ( Alces alces ) may be less contagious, or not contagious between live animals under field conditions. Th...

Prion diseases, including chronic wasting disease (CWD) in cervids, are fatal neurodegenerative disorders caused by the misfolding of cellular prion proteins. CWD is known to spread among captive and free-ranging deer in North America. In 2016, an outbreak of contagious CWD was detected among wild reindeer in Norway, marking the first occurrence of...

Chronic wasting disease is a fatal prion condition of cervids such as deer, elk, moose and reindeer. Secretion and excretion of prion infectivity from North American cervids with this condition causes environmental contamination and subsequent efficient lateral transmission in free-ranging and farmed cervids. Variants of cervid PrP exist that affec...

Prion diseases are a group of neurodegenerative, transmissible, and fatal disorders that affect several animal species. They are characterized by the conformational conversion of the cellular prion protein (PrP C ) into the pathological prion protein (PrP Sc ). In 2016, chronic wasting disease (CWD) gained great importance at European level due to...

The first case of CWD in Europe was detected in a Norwegian reindeer in 2016, followed later by two CWD cases in Norwegian moose. To prevent the potential spread of CWD to the EU, the European Commission (Regulation EU 2017_1972) implemented a CWD surveillance programme in cervids in the six countries having reindeer and or moose (Estonia, Finland,...

Our previous studies using gene-targeted mouse models of chronic wasting disease (CWD) demonstrated that Norway and North America cervids are infected with distinct prion strains that respond differently to naturally occurring amino acid variation at residue 226 of the prion protein. Here we performed transmissions in gene-targeted mice to investig...

Surveillance of wildlife diseases poses considerable logistical challenges compared to that of humans or livestock. Citizen science can enable broader coverage, but building an efficient disease monitoring system that relies on hunters is challenging. Chronic wasting disease (CWD) is a lethal and infectious prion disease of cervids. Improving surve...

Background Chronic wasting disease (CWD) is a prion disease of cervids first reported in North America in the 1960s. In Europe, CWD was first diagnosed in 2016 in a wild reindeer in Norway. Detection of two more cases in the same mountain area led to the complete culling of this partially confined reindeer population of about 2400 animals. A total...

Viral interference is a process where infection with one virus prevents a subsequent infection with the same or a different virus. This is believed to limit superinfection, promote viral genome stability, and protect the host from overwhelming infection. Mechanisms of viral interference have been extensively studied in plants, but remain poorly und...

Concern is mounting over the global emergence, expanding host range, and uncertain zoonotic potential of chronic wasting disease (CWD), a fatal, infectious disease of cervids caused by prions. Our previous studies using genetically modified CWD-susceptible mice showed that Norwegian and North American CWD are caused by different prion strains. Here...

Prions are infectious agents that replicate through the autocatalytic misfolding of the cellular prion protein (PrPC) into infectious aggregates (PrPSc) causing fatal neurodegenerative diseases in humans and animals. Prions exist as strains, which are encoded by conformational variants of PrPSc. The transmissibility of prions depends on the PrPC se...

Rabies is an important zoonotic disease with high fatality rates in animals and humans. In the Arctic, the Arctic fox (Vulpes lagopus) is regarded as the principal reservoir, but there is considerable debate about how the disease persists at the low population densities that are typical for this species. We describe an outbreak of rabies among Arct...

Prion diseases are fatal neurodegenerative disorders with known natural occurrence in humans and a few other mammalian species. The diseases are experimentally transmissible, and the agent is derived from the host-encoded cellular prion protein (PrP C ), which is misfolded into a pathogenic conformer, designated PrP Sc (scrapie). Aggregates of PrP...

Background: Chronic wasting disease (CWD) is a prion disease of cervids. In 2016, CWD was discovered for the first time in reindeer. The affected population was situated in Nordfjella mountain region in Norway. In an attempt to eradicate the disease, all reindeer in the region were culled during winter 2017-18. Because many sheep have their summer...

Reindeer pastoralism is a widespread practise across Fennoscandia and Russia. An outbreak of chronic wasting disease (CWD) among wild reindeer (Rangifer tarandus) poses a severe threat to the semi-domestic reindeer herding culture. Establishing surveillance is therefore key, but current models for surveillance of CWD are designed for wild cervids a...

Susceptibility of cervids to Chronic Wasting Disease (CWD), a prion disease, can be modulated by variations in the prion protein gene (PRNP), encoding the cellular prion protein (PrPC). In prion diseases, PrPC is conformationally converted to pathogenic conformers (PrPSc), aggregates of which comprise infectious prions. CWD has recently been observ...

Prions are infectious proteins causing fatal, transmissible neurodegenerative diseases of animals and humans. Replication involves template-directed refolding of host encoded prion protein, PrPC, by its infectious conformation, PrPSc. Following its discovery in captive Colorado deer in 1967, uncontrollable contagious transmission of chronic wasting...

Background Chronic wasting disease (CWD) is a rapidly spreading prion disorder affecting various species of wild and captive cervids. The risk that CWD poses to cohabiting animals or more importantly to humans is largely unknown. Methods In this study, we investigated differences in the capacity of CWD isolates obtained from 6 different cervid spe...

We report the first detection of chronic wasting disease (CWD) in Sweden, in three old female moose (Alces alces). Prions (PrPCWD) were detected in brain but not in lymph nodes. The findings are similar to previously described CWD cases in old moose in Norway, where a spontaneous origin is hypothesized.

Scrapie is a transmissible spongiform encephalopathy that occurs in sheep. Atypical/Nor98 scrapie occurs in sheep that tend to be resistant to classical scrapie and it is thought to occur spontaneously. The purpose of this study was to test the transmission of the Atypical/Nor98 scrapie agent in three genotypes of Suffolk sheep and characterize the...

Chronic wasting disease (CWD) is the transmissible spongiform encephalopathy or prion disease affecting cervids. In 2016 the first cases of CWD were reported in Europe in Norwegian wild reindeer and moose. The origin and zoonotic potential of these new prion isolates remain unknown. In this study to investigate zoonotic potential we inoculated brai...

International policy for the management of wildlife disease(s) plays an important role for concerted action, and changes to policy should be evidence‐based and updated as new evidence accumulates. Management of chronic wasting disease (CWD), the prion disease affecting cervids, is based on its highly contagious nature relative to most other prion d...

The successful mitigation of emerging wildlife diseases may involve controversial host culling. For livestock, ‘preemptive host culling’ is an accepted practice involving the removal of herds with known contact to infected populations. When applied to wildlife, this proactive approach comes in conflict with biodiversity conservation goals. Here, we...

1. The hypothesis of the study was that a high dietary starch level (HS) would lead to impaired gut health compared to a low-starch diet (LS) in Eimeria-challenged broilers. The effects of two diets with different starch to fat ratios on intestinal histomorphometry, Clostridium perfringens counts and toxin profile, necrotic enteritis prevalence and...

The DNA glycosylase Neil2 is a member of the base excision repair (BER) family of enzymes, which are important for repair of oxidative DNA damage. Specifically, Neil2 participates in repair of oxidized bases in single-stranded DNA of transcriptionally active genes. Mice with genetic ablation of Neil2 (Neil2−/−) display no overt phenotypes, but an a...

In "Porcine Prion Protein as a Paradigm of Limited Susceptibility to Prion Strain Propagation" by Espinosa et al. [J Infect Dis, doi:10.1093/infdis/jiz646], there was an error in Figure 2 and the footnote corresponding to Supplementary Figure 1 was missing. These have been corrected in the original article. (Figure Presented).

Background: Necrotic enteritis is a significant problem to the poultry industry globally and, in Norway up to 30% of Norwegian turkey grow-outs can be affected. However, despite an awareness that differences exist between necrotic enteritis in chickens and turkeys, little information exists concerning the pathogenesis, immunity, microbiota or expe...

Prion diseases are progressive and fatal, neurodegenerative disorders described in humans and animals. According to the “protein-only” hypothesis, the normal host-encoded prion protein (PrPC) is converted into a pathological and infectious form (PrPSc) in these diseases. Transgenic knockout models have shown that PrPC is a prerequisite for the deve...

Although experimental transmission of bovine spongiform encephalopathy (BSE) to pigs and transgenic mice expressing pig cellular prion protein (PrPC) (porcine PrP [PoPrP]-Tg001) has been described, no natural cases of prion diseases in pig were reported. This study analyzed pig-PrPC susceptibility to different prion strains using PoPrP-Tg001 mice e...

Background: Necrotic enteritis is a significant problem to the poultry industry globally and, in Norway up to 30 % of Norwegian turkey grow-outs can be affected. However, despite an awareness that differences exist between necrotic enteritis in chickens and turkeys, little information exists concerning the pathogenesis, immunity, microbiota or expe...

The emergence of CWD in Europe in 2016 and the first natural infection in wild reindeer warranted disease management. This led to the testing of 2424 hunted or culled reindeer during 2016–2018, from the infected subpopulation in the Nordfjella mountain range in Southern Norway. To identify any association between PRNP variation and CWD susceptibili...

Significance The origin of transmissible BSE in cattle remains unestablished. Sheep scrapie is a potential source of this known zoonotic. Here we investigated the capacity of sheep scrapie to propagate in bovine PrP transgenic mice. Unexpectedly, transmission of atypical but not classical scrapie in bovine PrP mice resulted in propagation of classi...

Chronic wasting disease (CWD) is a highly contagious prion disease affecting captive and free-ranging cervid populations. CWD has been detected in United States, Canada, South Korea and, most recently, in Europe (Norway, Finland and Sweden). Animals with CWD release infectious prions in the environment through saliva, urine and feces sustaining dis...

Article, in Norwegian, about CWD in Norway.

Abstract The European Commission asked EFSA for a Scientific Opinion: to revise the state of knowledge about the differences between the chronic wasting disease (CWD) strains found in North America (NA) and Europe and within Europe; to review new scientific evidence on the zoonotic potential of CWD and to provide recommendations to address the pote...

Infection patterns linked to age and sex are crucial to predict the population dynamic effects of diseases in long‐lived species. How such demographic patterns of infection arise is often multifactorial, although the cause is commonly seen as a combination of immune status as well as variation in pathogen exposure. Prion diseases are particularly i...

Background: Little information exists concerning the pathogenesis, immunity, microbiota or experimental reproduction of turkey necrotic enteritis. Necrotic enteritis in turkeys and chickens differ with regard to important aspects. The objective of this study was to contribute to the development of in vivo experimental models of necrotic enteritis i...

Chronic Wasting Disease (CWD) is a highly infectious, naturally occurring, transmissible spongiform encephalopathy (TSE, or prion disease) affecting many cervid species. CWD has been widely circulating in North America since it was first reported in 1967. In 2016, the first European case of prion disease in deer was reported and confirmed in Norway...

Chronic wasting disease (CWD) is a fatal contagious prion disease naturally occurringing cervids in North America. In 2016, CWD was detected in wild reindeer (Rangifer tarandus) and moose (Alces alces) in Norway. Here, we report the first known naturally infected wild Norwegian red deer (Cervus elaphus)

Chronic wasting disease (CWD) persists in cervid populations of North America and in 2016 was detected for the first time in Europe in a wild reindeer in Norway. We report the detection of CWD in 3 moose (Alces alces) in Norway, identified through a large scale surveillance program. The cases occurred in 13-14-year-old female moose, and we detected...

Molecular weight of protease-resistant core of abnormal form of prion protein (PrPres) fragments determined by epitope mapping, immunohistochemistry staining of moose brain tissues of a Norwegian moose with chronic wasting disease, Western blot analysis of PrPres from different brain areas brain of 3 Norwegian moose with chronic wasting disease, an...

Surveillance of wildlife diseases is logistically difficult, and imperfect detection is a recurrent challenge for disease estimation. Using citizen science can increase sample sizes, but it is associated with a cost in terms of the anatomical type and quality of the sample. Additionally, biological tissue samples from remote areas lose quality due...

Chronic Wasting Disease (CWD) was discovered in reindeer (Rangifer tarandus) and moose (Alces alces) in spring 2016, and in red deer (Cervus elaphus) in 2017. This was the first time the disease was detected in Norway and Europe. CWD, a transmissible spongiform en-cephalopathy (TSE), is a neurological and always fatal disease affecting deer species...

Gill disease in Atlantic salmon, Salmo salar L., causes big losses in the salmon farming industry. Until now, tools to cultivate microorganisms causing gill disease and models to study the gill responses have been lacking. Here we describe the establishment and characterization of two cell lines from the gills of Atlantic salmon. Atlantic salmon gi...

Abstract The European Commission asked EFSA for a scientific opinion on chronic wasting disease in two parts. Part one, on surveillance, animal health risk‐based measures and public health risks, was published in January 2017. This opinion (part two) addresses the remaining Terms of Reference, namely, ‘are the conclusions and recommendations in the...

Chronic wasting disease (CWD) is a relatively new and burgeoning prion epidemic of deer, elk, reindeer, and moose, which are members of the cervid family. While the disease was first described in captive deer, its subsequent discovery in various species of free-ranging animals makes it the only currently recognized prion disorder of both wild and f...

In April and May of 2016, Norway confirmed two cases of chronic wasting disease (CWD) in a wild reindeer and a wild moose, respectively. In the light of this emerging issue, the European Commission requested EFSA to recommend surveillance activities and, if necessary, additional animal health risk-based measures to prevent the introduction of the d...

Chronic wasting disease (CWD) is a fatal contagious prion disease in cervids that is enzootic in some areas in North America. The disease has been found in deer, elk and moose in the USA and Canada, and in South Korea following the importation of infected animals. Here we report the first case of CWD in Europe, in a Norwegian free-ranging reindeer...

Base excision repair (BER) is the major pathway for repair of oxidative DNA damage. Mice with genetic knockout of the BER enzyme Neil3 display compromised neurogenesis in the sub-ventricular zone of the lateral ventricle and sub-granular layer of the dentate gyrus of the hippocampus. To elucidate the impact of oxidative DNA damage-induced neurogene...

Bovine spongiform encephalopathy (BSE) created a global European crisis in the 1980s and 90s, with very serious health and economic implications. Classical BSE now appears to be under control, to a great extent as a result of a global research effort that identified the sources of prions in meat and bone meal (MBM) and developed new animal-testing...

Infectious salmon anaemia (ISA) is an important, systemic viral disease of farmed Atlantic salmon, Salmo salar L. Endothelial cells are the main target cells for highly virulent HPR-deleted ISA virus (ISAV) types. Here we examine the pathogenesis of non-virulent ISAV HPR0 infections, presenting evidence of an epithelial tropism for this virus type,...

RT-qPCR of gills and IHC on formalin fixed paraffin embedded gills from farm II. ISAV segment 8 and ELF RT-qPCR Ct values and IHC using antibody to ISAV NP on gills from farm II. All fish were positive for HPR0 by RT-qPCR, but only 17 of 40 were positive by IHC. +: positive labelling of epithelial cells in the gill. -: negative, nt: not tested. (PD...

Since future conventional broiler production can no longer rely upon in-feed antimicrobials (anticoccidials and antibiotic growth promoters), understanding the most important non-antimicrobial factors influencing occurrence of necrotic enteritis (NE) in poultry will become urgent. Solid population-based data on NE occurrence are scarce. Additionall...

Establishment of cell culture to study gill diseases in Atlantic salmon

Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential o...

Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These...

Hypergastrinaemia is observed commonly in human patients with gastric carcinoma and is associated with atrophic gastritis and Helicobacter pylori infection, both of which predispose to development of gastric tumours. Increased expression of gastrin is also described as a prognostic indicator for gastric carcinoma in man. Gastric carcinoma is rare i...

The detailed mechanisms of prion-induced neurotoxicity are largely unknown. Here, we have studied the role of DNA-damage caused by reactive oxygen species in a mouse scrapie model by characterizing prion disease in the ogg1(-/-)mutyh(-/-) double knock-out, which is compromised in oxidative DNA base excision repair (BER). Ogg1 initiates removal of t...

Prion diseases are classically characterized by the accumulation of pathological prion protein (PrP(Sc)) with the protease resistant C-terminal fragment (PrP(res)) of 27-30 kDa. However, in both humans and animals, prion diseases with atypical biochemical features, characterized by PK-resistant PrP internal fragments (PrP(res)) cleaved at both the...

Characterization of Nor98 PrPres fragments. Comparative PK titration in Nor98 and classical scrapie. PK digestion curves of classical scrapie (n = 4) and Nor98 (n = 4) with concentrations of PK ranging from 0.006 to 6.4 mg/ml. Replica blots were probed with SAF84 and P4 and selected fragments were quantified. Representative WB are shown in the left...

Table with sheep and goat samples. (DOC)

PrPres phenotypes in GSS P102L cases. Western blot of the two GSS P102L cases (#15 and #16, Table 1). Samples were treated with 50 µg/ml PK and membranes were probed with F89. MW markers are shown in kilodaltons on the left. (TIF)

Derivation of the N and C terminal PK cleavage sites from epitope mapping data. The PK cleavages were derived taking into account the epitope mapping data, summarised in Table 2, the known N-terminal cleavage sites in sCJD [67] and in scrapie or sheep BSE [74], [75], and the potential cleavage sites cleaved by PK in the corresponding human and shee...

Prion diseases such as scrapie in small ruminants, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in man, are fatal neurodegenerative disorders. These diseases result from the accumulation of misfolded conformers of the host-encoded prion protein (PrP) in the central nervous system. To date naturally-occurring...

Prion diseases are diagnosed by the detection of their proteinase K-resistant prion protein fragment (PrP(Sc)). Various biochemical protocols use different detergents for the tissue preparation. We found that the resistance of PrP(Sc) against proteinase K may vary strongly with the detergent used. In our study, we investigated the influence of the...

Quantitative analysis of the PrPres phenotype in atypical scrapie affected tg338 mice. Molecular mass (y-axis, ±SD) and relative quantities of PrPres bands (numbers [%] at the right side of each dot) are depicted as means from at least five mice per isolates following SDS-PAGE using 4–20% gradient gels and monoclonal antibody P4. (TIF)

Western blot banding patterns in the brains of sham-inoculated mice. (A) Tg338 mice inoculated with TSE-negative sheep brain show variable banding patterns after treatment with PK (50 µg/ml). Survival times (in days) of individual mice are indicated on the top. The picture on the left shows an atypical scrapie affected mouse-brain sample (S7/CS) fo...

Scheme of the neuroanatomical PrPd distribution in groups of tg338 mice inoculated with different scrapie isolates. (A) Presentation of the neuroanatomical structures investigated: cortex (cx), cingulum (cg), cerebral white matter (cw), corpus callosum (cc), caudate putamen (pu), septal nuclei (se), anterior commissure (ac), ventral pallidum (vp),...

The pathobiology of atypical scrapie, a prion disease affecting sheep and goats, is still poorly understood. In a previous study, we demonstrated that atypical scrapie affecting small ruminants in Switzerland differs in the neuroanatomical distribution of the pathological prion protein (PrP(d)). To investigate whether these differences depend on ho...

Gastric juice is a unique combination of hydrochloric acid and the proteolytic enzyme pepsin. Its main function is to inactivate ingested microorganisms. Prions cause fatal transmissible degenerative encephalopathies in animals and man. These diseases have attracted attention due to the proposed link between bovine spongiform encephalopathy in catt...

Although prion diseases, such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protea...

PrPSc Western Blot profile and vacuolar lesion profile in tg338 mice inoculated with various tissues from an Atypical/Nor98 scrapie and classical scrapie affected sheep. (A) PrPSc Western Blot profile. Lane 1: posterior brainstem from a PG127 classical scrapie affected sheep (case 12). Lane 2: brain from a 700 days old negative control tg338 mouse....