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lunes, 16 de marzo de 2015

Prions - Not Your Immunologist’s Pathogen.

A colleague and fellow immunologist, we will call her “Anne,” lifts her index and middle fingers on each hand and bows them in “air quotes” as she says prion “immunology” during my student’s thesis committee meeting. Anne says she works on “malaria, a real pathogen that elicits a real immune response.” Now, I am pretty sure Anne believes prions exist, but does she have a point about the immune response they elicit? The answer may surprise you.
Prions are remarkable, enigmatic pathogens that are quite different than most disease-causing entities. According to the prion hypothesis, prions are infectious agents devoid of instructional nucleic acid [1]. They propagate themselves without a genetic code, instead enciphering their infectious nature structurally, within the protein conformation itself. Mounting evidence supports the prion hypothesis, including the generation of infectious prions from purified recombinant protein [2]. Soon after Prusiner coined the term “prion,” his and Charles Weissmann’s labs discovered that a cellular gene encodes the prion agent [3]. Strangely, though, Prusiner had already demonstrated that infectious prions did not include nucleic acid, suggesting that prions infect without transmitting the gene encoding them. So attention turned to the host, in which this gene also encodes a normal form of the agent, called cellular prion protein (PrPC), that was later shown to be absolutely required to generate both genetic and acquired prion diseases [4]. And so, all the armchair immunologists reading this article right now pause and say, “Wait a minute…” while Anne chimes in with “prion immunology.” Here we go.

Zabel MD, Avery AC (2015) Prions—Not Your Immunologist’s Pathogen. PLoS Pathog 11(2): e1004624. doi:10.1371/journal.ppat.1004624
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