virology blog
About viruses and viral disease
TWiV revisits chronic wasting disease of cervids and the ability of the prions to infect meadow voles and raccoons, and the suggestion that stochastic assembly of influenza virus particles may play a role in phenotypic diversity.
Hosts: Vincent Racaniello, Dickson Despommier, Rich Condit, and Amy Rosenfeld
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The sages of TWiV explain how chronic wasting disease of cervids could be caused by spontaneous misfolding of prion protein, and the role of the membrane protein Axl in Zika virus entry into cells.
You can find TWiV #426 at microbe.tv/twiv, or listen below.
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Chronic wasting disease is a prion disease of cervids (deer, elk, moose) that is potentially a threat to human health. A role for environmental prion contamination in transmission is supported by the finding that plants can take up prions from the soil and transmit them to animals.
A concern is that prions of chronic wasting disease could be transmitted to cows grazing in pastures contaminated by cervids. Consumption of infected cows would then pass the disease on to humans. When deer are fed prions they excrete them in the feces before developing clinical signs of infection, and prions can also be detected in deer saliva. In the laboratory, brain homogenates from infected deer can transmit the disease to cows.
To determine whether prions can enter plants, wheat grass roots and leaves were exposed to brain homogenates from hamsters that had died of prion disease. The plant materials were then washed and amounts of prions were determined by protein misfolding cyclic amplification. Prions readily bound these plant tissues, at low concentrations and after as little as 2 minutes of incubation. Mouse, cervid, and human prions also bound to plant roots and leaves. When living wheat grass leaves were sprayed with a 1% hamster brain homogenate, prions could attach to the leaves and be detected for 49 days.
To determine if prions in plants could infect animals, plants were exposed to brain homogenates, washed thoroughly, and then fed to hamsters. The positive control for this experiment was to feed hamsters the brain homogenates. All animals fed infected plants or brain homogenates succumbed to prion disease.
Plants can also take up prions from animal waste. This conclusion was reached by incubating leaves and roots for 1 hour with urine or feces obtained from prion-infected hamsters or cervids. Prions were readily detected in these samples, even after extensive washing.
Experiments were also done to examine whether plants could take up prions from the soil. Barley grass plants were grown on soil that had been mixed with hamster brain homogenate, and then 1-3 weeks later, stem and leaves were assayed for the presence of prions. Small amounts of prions were detected in stems from all plants, while 1 in 4 plants contained prions in leaves, at levels that should be able to infect an animal.
These results show that prions can bind to plants and be taken into the roots, where they may travel to the stem and leaves. Therefore it is possible that prions excreted by deer could pass on to other animals, such as grazing cows, or even humans consuming contaminated plants (illustrated – image credit). Cooking plants will not eliminate infectivity, just as cooking contaminated beef did not halt the spread of bovine spongiform encephalopathy. Keeping cervids out of grazing or growing fields should be considered as a way to manage the risk of prions entering the human food chain.
Chronic wasting disease (CWD) is a prion disease of cervids (deer, elk, moose). It was first detected in Wyoming and Colorado, and has since spread rapidly throughout North America (illustrated; image credit). Because prions that cause bovine spongiform encephalopathy (BSE, mad cow disease) are known to infect humans, there is concern that CWD might also cross the species barrier and cause a novel spongiform encephalopathy. Recent experimental results suggest that CWD prions are not likely to directly infect humans.
The prion protein PrPC is encoded by the prnp gene, which is essential for the pathogenesis of transmissible spongiform encephalopathies (TSEs). Transgenic mice have been used to understand the species barrier to prion transmission. When mice are inoculated with human prions, few animals develop disease and the incubation periods are over 500 days. When the mouse prnp gene is replaced with the human gene, the mice become uniformly susceptible to infection with human prions and the incubation period is shorter. The species barrier to prion transmission is therefore associated with differences in the prion protein sequence between host and target species.
Mice have been used to understand whether CWD prions might be transmitted to humans. Mice are not efficiently infected with CWD prions unless they are made transgenic for the cervid prnp gene. Four different research groups have found that mice transgenic for the human prnp gene are not infected by CWD prions. These findings suggest that CWD prions are not likely to be transmitted directly to humans. However, changing four amino acids in human prnp to the cervid sequence allows efficient infection of transgenic mice with cervid prions.
Another concern is that prions of chronic wasting disease could be transmitted to cows grazing in pastures contaminated by cervids. Prions can be detected in deer saliva and feces, and contamination of grass could pass the agent on to cows. In the laboratory, brain homogenates from infected deer can transmit the disease to cows. Therefore it is possible that cervid prions could enter the human food chain through cows.
A further worry is that BSE prions shed by cows in pastures might infect cervids, which would then become a reservoir of the agent. BSE prions do not infect mice that are transgenic for the cervid prnp gene. However, intracerebral inoculation of deer with BSE prions causes neurological disease,  and the prions from these animals can infect mice that are transgenic for the cervid prnp gene. Therefore caution must be used when using transgenic mice to predict the abilities of prions to cross species barriers.
Although the risk of human infection with CWD prions appears to be low, hunters should not shoot or consume an elk or deer that is acting abnormally or appears to be sick, to avoid the brain and spinal cord when field dressing game, and not to consume brain, spinal cord, eyes, spleen, or lymph nodes. No case of transmission of chronic wasting disease prions to deer hunters has yet been reported.