Prions Survive Crow Guts
Mad cow disease, kuru, chronic wasting disease—all of these ghastly illnesses are caused by prions--misfolded proteins in the brain, which are more technically known as transmissible spongiform encephalopathies (TSEs). Once a prion infection sets in, the results are gruesome. Loss of muscle control, hallucinations, general neurological meltdown . . . the symptoms of prion disorders can lead to truly tragic and painful deaths, all ultimately due to a few key misshapen proteins (see this neat interactive animation for a refresher on protein folding).
Despite the Hollywood-worthy symptoms of prion disorders, the most disturbing part of a TSE is the ‘T’ part: “transmissible.” We have talked about transmissible cancers on this blog before, and transmissible encephalopathies are also both lethal and dramatic. The specter of such a devastating brain disease being passed from one individual to another seems like something out of a cheap horror novel—and yet it happens every day in nature.
Although we usually think about TSE infections resulting from direct contact with an infected animal, what if you could become infected simply from exposure to feces left by an exposed vector animal? A recent PLoS ONE paper describes a study on passive transmission of infectious prions by crows, highlighting a form of disease spread that is little-known yet potentially very important from a disease ecology perspective. What happens when prions hitch a ride on aerial hosts? It sounds more like a bioterrorism plot, but is actually a result of normal food chain dynamics.
Crows are notorious scavengers, feeding upon carcasses of animals that may have died from any number of traumas or diseases. Further, it is already known that TSEs can be contracted from the consumption of infected flesh. For example, Kuru, a lethal form of encephalopathy found amongst the Fore people of Papua New Guinea, is transmitted through ritual cannibalism during funeral rites. Given that prion disorders such as chronic wasting disease are not uncommon amongst North American wildlife, there is a realistic possibility that scavengers will be exposed to TSE-infected flesh. The potentianl risks to the scavengers themselves are obvious, but the hazards may extend even further. Will the prion strains remain infective after the infected food has been digested and excreted, and can those excreted prions go on to infect other animals? The answer to these questions are critically important for understanding the role that avian scavengers may play in transporting pathogens from place to place after feeding on carrion.
In the recent experiment reported by VerCauteren and colleagues, twenty American Crows (Corvus brachyrhynchos) were fed mouse brain material infected with scrapie prions, to simulate feeding upon infected carcasses (VerCauteren et al. 2012). Next, the researchers obtained feces samples from the birds, and injected extracts from the feces into lab mice to determine whether the disease remained infectious after passing through the birds’ digestive systems. Another set of mice was injected directly with infected mouse brain material—the same substance that had been fed to the crows.
The results were striking: all of the mice that survived for at least three days after the inoculations (there were a handful of fatalities due to toxicity from uric acid in the bird feces) exhibited neurological dysfunctions characteristic of prion disorders, and tested positive for prion infection subsequent to their deaths. Mice that were injected directly with mouse brain material developed neurological symptoms approximately 15 days earlier than those infected through crow fecal material, suggesting that indirect infection may provide a smaller dose, although still enough to be ultimately lethal. Between 83-100% of the crows were estimated to produce feces capable of infecting mammals with the prion disorder.
It is also noteworthy that this study was designed to provide conservative estimates of post-digestion prion infectivity. The type of scrapie that was used in this study, the RML Chandler strain, is more sensitive to enzymatic activity than many others. This means that more robust strains may be even more infective after ingestion and excretion by birds, an ominous scenario indeed.
The takeaway message was that prions can remain lethally infectious after they have passed through the entire digestive tract of an avian scavenger, and the implications of these results are important and fascinating. Crows produced infective feces within four hours of feeding, and in that amount of time a crow can travel a nontrivial distance from its initial feeding site, turning a TSE outbreak from a local event spread by direct contact between individuals into a much broader ordeal across the landscape. A crow can drop feces while in flight and infect multiple other animals even after the bird itself has continued on its merry way. Given that this initial experiment was conducted under lab conditions, it will be interesting to see further research on how long prions remain infective in the feces under different environmental conditions will provide additional insights into how avian scavengers may affect the transmission dynamics of these diseases.
VerCauteren KC, Pilon JL, Nash PB, Phillips GE, & Fischer JW (2012). Prion remains infectious after passage through digestive system of American crows (Corvus brachyrhynchos). PloS one, 7 (10) PMID: 23082115