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Science Advances

Science Advances

Limited transmission of cervid prions to nonhuman primates provides insights...

Samia Hannaoui, Sandra Pritzkow, Wiebke M. Jürgens-Wemheuer, Dirk Motzkus, Joo- Hee Wälzlein, Karla A. Schwenke, Yo-Ching Cheng, Hanaa Ahmed Hassan, Irina Zemlyankina, Kylee Drever, Michael Beekes, Walter J. Schulz-Schaeffer, Christiane Stahl- Hennig, Sabine Gilch, Claudio Soto, Stefanie Czub, Hermann M. Schätzl ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ Chronic wasting disease (CWD) is an expanding prion disease of cervids. CWD prions persist in the environment, areshed in excreta, and accumulate in tissues of infected cervids, raising concerns about its zoonotic potential. Usingcynomolgus macaques, we explored the zoonotic potential of CWD. Although most inoculated macaques remainedasymptomatic, sensitive in vitro prion amplification assays revealed low levels of prions in macaque tissues. Inocula-tion of transgenic mice and bank voles with macaque tissues induced prion disease, achieving 100% transmissionrates upon serial passage. One interpretation of these findings is that CWD prions retain infectivity across speciesand that primate infection may manifest atypically while still enabling transmission. Our results challenge earlierconclusions that minimize the zoonotic risk of CWD and underscore the need for continued surveillance.

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MDPI Pathogens

MDPI | Pathogens

A Neuronal Cell Line Model for Studying Camel Prions

Basant Abdulrahman, Shabboo Rahimi Aqdam, Matteo Mosca, Hanaa Ahmed-Hassan, Melissa Razcon-Echeagaray, Lia Popa, Sabine Gilch, Baaissa Babelhadj, Gabriele Vaccari, and Hermann M. Schätzl ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ Prion diseases are fatal neurodegenerative disorders that affect humans and animals, caused by the conformational conversion of the normal cellular prion protein (PrPC) into its misfolded, infectious isoform PrPSc. Recently, camel prion disease (CPrD) was identified in dromedary camels (Camelus dromedarius) in Algeria. Due to the potential implications for animal and human health, as well as the possible socio-economic impact in Mediterranean regions where camels play a pivotal role as a source of food, in-depth characterization of camel prions is important to increase our understanding of camel prion disease. We developed a neuronal cell line model for studying the molecular features of camel prion infection. We genetically edited mouse neuronal CAD5 cells to generate CAD5 PrP knockout (KO) cells. We then used lentiviral transduction to generate CAD5 cells expressing camel PrP (CAD5-camel-PrP). Following infection of these cells with a CPrD-positive camel brain homogenate, we observed PrPSc signals at various passages, as indicated by immunoblotting analysis. RT-QuIC (Real-Time Quaking-Induced Conversion) assays further supported these findings, demonstrating transient prion conversion activity in the CPrD-infected CAD5-camel-PrP cells. Taken together, our data describe the first neuronal cell line permissive to camel prion infection, a novel in vitro tool for mechanistic studies of camel prion disease.

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PLOS Pathogens

PLOS | Pathogens

Prion shedding is reduced by chronic wasting disease vaccination

Hanaa Ahmed Hassan, Dalia Abdelaziz, Yo-Ching Cheng, Kevin Low, Shirley Phan, Byron Kruger, Chimone Dalton, Lech Kaczmarczyk, Walker Jackson, Sabine Gilch, Hermann Schatzl‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ Chronic wasting disease (CWD) is a strictly fatal and highly contagious prion disease of wild and farmed cervids currently expanding in North America. Prion diseases are caused by conversion of the cellular prion protein to its pathological isoform PrPSc. Vaccination is considered a promising strategy to contain CWD, even though prion diseases do not show classical immune responses. For CWD containment, it is important that vaccines reduce shedding of prions in excreta, a major contributor to transmission. Here, we tested the effect of vaccines on prion shedding in feces and urine by vaccinating and prion infecting knock-in mice that recapitulate CWD pathogenesis as found in cervids. Vaccination reduced or even prevented CWD shedding in feces and urine collected between 30-90% of incubation time to disease. This is the first report showing that prion shedding can be blocked in a prion disease. For CWD specifically it may reduce the environmental prion burden and break the disease transmission cycle.

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More Publications From the Schaetzl Lab

In the News

  1. UCalgary News

    UCalgary researchers at work on a vaccine against a fatal infectious disease affecting deer and potentially people

     

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  2. CBC News | Edmonton

    Chronic wasting disease threatens deer, elk — and maybe humans, new research says ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  

     

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  3. CTV News | Calgary

    Alberta uses hunters to reduce deer numbers in effort to slow spread of debilitating disease‎ ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎ 

     

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  4. The Western Producer

    CWD may have ability to jump to humans ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎ 

     

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  5. Bovine Veterinarian

    University of Calgary Vaccine Protects Against CWD ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎ 

     

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