prions

[Joao Vasconcelos Costa]

Ian A. York wrote:
> 
> In article <316B77D5.7FEC at pen.gulbenkian.pt>,
> Joao Vasconcelos Costa  <jcosta at pen.gulbenkian.pt> wrote:
(...)
> >Another finding that seems to me difficult to reconcile with the prion
> >model is the neuronal pathway of spread of infectivity from the spleen
> >to the central nervous system. Any ideas about this?
> 
> I've assumed that the spread to the brain is within cells of the
> reticuloenbdothelial system - via monocytes/macrophages.  I suppose it
> could be neuronal as well, or instead (passive axonal transport would
> probably carry the particles to the brain) but it seems simpler to assume
> that they prion is being carried by something to the brain, no?
> 
> Ian

Data in favor of a neuronal spread were reviewed by Liberski (Arch.
Virol., suppl 6, 1993, pp 95-100.

The agent is not passively transported from the primary infected organ 
(spleen and other lymphoid organs) to the brain. It replicates in the 
spinal cord neurons, apparently starting at the neurons corresponding to 
the spleen nerves. Replication in the medula takes place in an orderly 
way, from the thoracic cord to the cervical, at a speed of 0.5-1 mm/day.

In experiments of intraocular inoculation, the cerebral lesions start
to appear at the optical zones of the brain.
The well known case of CJD after cornea transplant also seems to argue
in favor of a neural spread.

How does the agent travel? Along the axons? along the myelin sheet?
via glial cells? In any case, it should be able to cross the membranes 
and be transferred from cell to cell, since it replicates along the 
spread path. A receptor for circulating prions has been postulated but, 
as far as I remember, secretion by infected cells has not been 
demonstrated. The precipitation as fibrils or amyloid plaques seems to 
be against secretion.

Joao
 
-- 
*****   JOAO VASCONCELOS COSTA, MD, PhD
*****   Instituto Gulbenkian de Ciencia - Oeiras, Portugal
*****   mailto:jcosta at pen.gulbenkian.pt
*****   http://www.pen.gulbenkian.pt/v2/jvc.html