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Prion protein: a pattern recognition receptor for viral components and uric acid responsible for the induction of innate and adaptive immunity.

Abstract：

:Prion protein, known as Prp(c), is a GPI-anchored membrane bound glycoprotein ubiquitously expressed in the body. To date, the precise nature of its physiological role remains a mystery. The prion protein's presence on neurons and immune effector cells suggests a dual neurological and immunological function. Some consensus exists regarding the proposed involvement of Prp(c) in neurodevelopment, where it would serve to mediate interactions between the extra-cellular matrix (ECM) and the neuron. There is also evidence that Prp plays a part in immunity, although the exact nature of the role remains unclear. Interestingly, a role in both immunity and development is a functional division seen in other types of receptors, most notably the Toll Receptor. In mammals, toll-like receptors (TLRs) are partly responsible for both innate and adaptive immune activity. However, recently several TLR independent pathways have been identified that initiate such responses. Unfortunately, receptors for such pathways remain unidentified. But based upon its functional homology to Toll Receptors, its known interactions with several viruses, and its possible downstream effector proteins, it is proposed that Prp(c) represents a new type of pattern recognition receptor responsible for TLR-independent induction of myeloid dendritic cell and macrophage maturation and later T-cell activation. From what is known of the ligands for the prion protein, it is proposed that this response would be initiated via the binding of uric acid, viral RNA, or viral structural proteins to Prp(c). It will further be proposed that Prp(c)'s ability to interact with viral components stems from its evolutionary origin as a horizontally transferred gene from an early RNA virus. Finally, Prp(c)'s functional role in immunity will be related to the pathophysiology of TSEs, with observations made concerning immune response to infection and agent composition.

journal_name

Med Hypotheses

journal_title

Medical hypotheses

authors

McBride SM

doi

10.1016/j.mehy.2005.02.038

keywords:

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

570-7

issue

eissn

0306-9877

issn

1532-2777

pii

S0306-9877(05)00156-8

journal_volume

pub_type

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Prion protein: a pattern recognition receptor for viral components and uric acid responsible for the induction of innate and adaptive immunity.