• JID 2010:201 (1 June) • 1615
E D I T O R I A L C O M M E N TA R Y
A Kiss of a Prion: New Implications for Oral Transmissibility
Bianca Da Costa Dias and Stefan F. T. Weiss
School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.
(See the report by Maddison et al, on pages 1672–1676.)
Received 11 February 2010; accepted 23 February 2010;
electronically published 19 April 2010.
Potential conflicts of interest: none reported.
Financial support: Deutsche Forschungsgemeinschaft, Germany
Reprints or correspondence: Prof Stefan F. T. Weiss, School
of Molecular and Cell Biology, University of the Witwatersrand,
Private Bag 3, 2050 Wits, Johannesburg, South Africa (stefan
The Journal of Infectious Diseases
? 2010 by the Infectious Diseases Society of America. All
There is no doubt about it: prions—in-
fectious particles composed mainly if not
entirely of misfolded protein (scrapie-type
prion protein [PrPSc]), which arethecaus-
ative agents of transmissible spongiform
encephalopathies (TSE) such as scrapie,
variant Creutzfeldt-Jakob Disease (vCJD),
and bovine spongiform encephalopathy
(BSE)—are transmissible [1–3]. These
agents may be introduced via intracere-
bral, intravenous, intraperitoneal, or in-
traventricular infection, and recent re-
search indicates that oral transmission
may also occur. The last mode of trans-
mission is of particular interest because it
indicates that the consumption of meat
and other products derived from animals
experiencing prion disorders may pose a
that, in addition to meat, bodily fluids
such as blood, saliva, feces, and milk may
well be risk factors for possible transmis-
sion of TSEs to humans. Successful oral
transmission among different animal spe-
cies (interspecies) has been demonstrat-
ed. However, species specificity, the “spe-
cies barrier,” and the mode of transmis-
sion must be taken into account and may
explain why cattle, sheep, goats, mink,
and mice are successfully orally infected
with bovine scrapie-type prion protein
(bovPrPSc), whereas the ingestion of
bovPrPScby pigs, poultry, and cervids
such as elk and deer fails to cause disease
. Humans are also thought to be sus-
ceptible to oral infection by bovPrPScby
means of contaminated bovine products
(eg, meat pies), and this is believed to be
the manner in which the zoonotic disease
vCJD originated .
But where do prions hide in the body?
vous system, particularly in the brain and
the lymphoreticular system , as well as
in other tissues such as muscle . Fur-
thermore, the presence of these infec-
tious agents in bodily excretions and se-
cretions is a major cause for concern,
because it enhances the risks of trans-
missibility. Prions have been identified in
feces of asymptomatic deer  and in the
blood, saliva, and urine of deer with
chronic wasting disease [7, 8]. PrPSchas
also been detected in the salivary glands
of scrapie-affected sheep .
The report by Maddison et al  in
this issue of the Journal describes for the
first time, to our knowledge, the secretion
of prions into the oral cavityofsheep.The
centrate prions, in conjunction with serial
protein misfolding cyclic amplification, or
sPMCA, a method to amplify and detect
the presence of very low concentrationsof
PrPSc. Serial protein misfolding cyclic am-
plification has numerous applications,
such as the sensitive detection of patho-
logical prions , later application for in
vitro generation of prions , and de-
tection of prions in body fluids such as
blood from scrapie-infected hamsters
; the last example succeeded even in
et al  used this technique to demon-
strate that prions are present in buccal
swab samples obtained from sheep with
preclinical scrapie infections.
However, one must pose the following
question: how do ingested infectiousPrPSc
prions reach the mucus and saliva? After
oral ingestion, prions are thought to be
taken up first by Peyer patchesbeforethey
disseminate through gut-associated lym-
phoid tissues, the lymphoreticular system,
the vagus nerve, and the enteric nervous
system, after which they enter the central
nervous system . Internalization of
prions in the intestine is thought to be
performed by M-(microfold) cells 
and by enterocytes, which internalize
bovPrPScdependent on the prion receptor
Maddison et al  suggest, according
to their data, that prions areabletospread
glands and epithelia within a period of 9
months. This route explains the occur-
rence of prions in saliva and the shedding
of prions into the oral cavity.
The transmissibility of scrapie among
sheep (intraspecies) is well recognized. It
must be emphasized thathorizontaltrans-
fer (from one individual to another) of
scrapie is the main route of infection, be-
mother to offspring via milk or placental
tissue occurs infrequently. Thus, in view
of the report by Maddison et al, the oral
transmissibility of prions among sheep
at University of Witwatersrand on April 10, 2014
1616 • JID 2010:201 (1 June) • EDITORIAL COMMENTARY Download full-text
may serve as a major route for horizontal
scrapie transfer. This occurrence is plau-
sible because sheep often lick each other.
Maddison et al  indicate that, because
of the similarities in prion tissue distri-
bution, their implications for the oral
transmission of ovine scrapie might be
true for other prion diseases, such as cer-
vid chronic wasting disease and human
vCJD. If this is true for humans, a kiss of
a prion may sometimes have lethal
We thank the Deutsche Forschungsgemein-
schaft (DFG) grant WE 2664/2–1, Germany and
the National Research Foundation (NRF), South
Africa, for financial support. We thank Professor
Juergen Richt, Kansas State University, United
States, for a critical reading of this paper.
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