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Cellulose ether treatment in vivo generates chronic wasting disease prions with reduced protease resistance and delayed disease progression
Author(s) -
Hannaoui Samia,
Arifin Maria Immaculata,
Chang Sheng Chun,
Yu Jie,
Gopalakrishnan Preetha,
Dohura Katsumi,
Schatzl Hermann M.,
Gilch Sabine
Publication year - 2020
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14877
Subject(s) - chronic wasting disease , in vivo , inoculation , biology , protease , in vitro , genetically modified mouse , virology , persistence (discontinuity) , transgene , microbiology and biotechnology , disease , prion protein , immunology , medicine , enzyme , biochemistry , scrapie , gene , geotechnical engineering , engineering
Chronic wasting disease (CWD) is a prion disease of free‐ranging and farmed cervids that is highly contagious because of extensive prion shedding and prion persistence in the environment. Previously, cellulose ether compounds (CEs) have been shown to significantly extend the survival of mice inoculated with mouse‐adapted prion strains. In this study, we used CEs, TC‐5RW, and 60SH‐50, in vitro and in vivo to assess their efficacy to interfere with CWD prion propagation. In vitro , CEs inhibited CWD prion amplification in a dose‐dependent manner. Transgenic mice over‐expressing elk PrP C (tgElk) were injected subcutaneously with a single dose of either of the CEs, followed by intracerebral inoculation with different CWD isolates from white tailed deer, mule deer, or elk. All treated groups showed a prolonged survival of up to more than 30 % when compared to the control group regardless of the CWD isolate used for infection. The extended survival in the treated groups correlated with reduced proteinase K resistance of prions. Remarkably, passage of brain homogenates from treated or untreated animals in tgElk mice resulted in a prolonged life span of mice inoculated with homogenates from CE‐treated mice (of + 17%) even in the absence of further treatment. Besides the delayed disease onset upon passage in TgElk mice, the reduced proteinase K resistance was maintained but less pronounced. Therefore, these compounds can be very useful in limiting the spread of CWD in captive and wild‐ranging cervids.