A team with members of Université Paris-Saclay examines how infectious proteins responsible for the mad cow outbreak are transmitted and expressed—results matter to public health.
Variant Creutzfeldt-Jakob disease (vCJD) is a rare but serious and fatal brain disorder. The first time this disease became apparent was in the 1980’s and 1990’s when the mad cow disease outbreak struck the UK. It’s believed that vCJD is caused by the ingestion of infectious prions, proteins that appear to be abnormally folded and are destructive in their nature. In the case of the mad cow outbreak, cows had been fed with food which had been contaminated by prions which led to the manifestation of the disease known as “bovine spongiform encephalopathy” in cattle. When humans then consumed meat products derived of cows infected with that disease, some developed variant Creutzfeldt-Jakob disease which has affected about 200 people since 1995.
In 2008, a British study analysed the appendices of over 32,000 anonymous donors and revealed that the abnormal prion protein that causes vCJD were found in 16 people which translates to a prevalence of about 1 in 2000. Researchers believe that in some people, vCJD can take decades to express itself and in others it may stay dormant permanently making them silent carriers. At the time, the risks associated with the possibility of being able to transmit these proteins from human to human via blood transfusions was not well understood. Though special precautions were taken, particularly in the UK, it is possible that over 1000 blood donations per year were contaminated.
Now, a recent study led by Emmanuel Comoy and other researchers at organizations that are part of Université Paris-Saclay, took a closer look at the risk of transmitting the infection via blood transfusions and blood related material. Researchers used two different methods to transmit variant Creutzfeldt-Jakob disease to mice and monkeys. One method was similar to a standard blood transfusion, using blood from an infected animal and the other involved injecting soluble infected brain tissue into the mice and monkeys. This last approach is often used in prion studies to mimic infectious blood.
Researchers found that not all animals developed vCJD and in cases where animals had received leukodepleted blood, where white blood cells had been removed, no vCJD was present. This is reassuring since this has become standard practice for human blood donation and transfusion. However they uncovered some other results which were less comforting, a significant proportion of the animals developed fatal neurological symptoms which differed from what we know as vCJD. This was observed in both the animals that had received injections of soluble brain tissue and those that received standard blood transfusions. What this tells us is that prion infections stemming from incidences like the mad cow outbreak may have the ability to cause neurological disorders other than vCJD in humans that are harder to detect and that we have yet to fully understand. It also suggests that the way an individual becomes infected could also affect the way disease manifests.
This eye-opening study is valuable to efforts in public health that are monitoring infectious diseases and keeping a close eye on how to mitigate the risk of their transmission. Researchers are eager to continue learning more about the various types of prion-based disorders that may exist.
More information: read the original scientific article Comoy, Emmanuel E., et al. “Experimental Transfusion of Variant CJD-Infected Blood Reveals Previously Uncharacterised Prion Disorder in Mice and Macaque.” Nature Communications, vol. 8, no. 1, 2 Jan. 2017, doi:10.1038/s41467-017-01347-0.
 Organizations that took part in this research are members of Université Paris-Saclay. They include: Commissariat à l’énergie atomique et aux énergies alternatives (CEA); Assistance Publique Hôpitaux de Paris (AP-HP); Centre national de la recherche scientifique (CNRS); Institut national de la santé et de la recherche médicale (Inserm); Institut national de la recherche agronomique (Inra); École nationale vétérinaire de Toulouse (ENVT); Institut Pasteur and MacoPharma.