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From: TSS ()
Subject: Re: Interspecies Transmission of Chronic Wasting Disease Prions to Squirrel Monkeys (Saimiri sciureus)
Date: October 19, 2005 at 11:21 am PST

In Reply to: Interspecies Transmission of Chronic Wasting Disease Prions to Squirrel Monkeys (Saimiri sciureus) posted by TSS on October 19, 2005 at 8:33 am:

JOURNAL OURNAL OF VIROLOGY IROLOGY, Nov. 2005, p. 13794–13796 Vol. 79, No. 21
0022-538X/05/$08.00 !0 doi:10.1128/JVI.79.21.13794–13796.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Interspecies Transmission of Chronic Wasting Disease Prions to
Squirrel Monkeys (Saimiri sciureus sciureus)
Richard F. Marsh, 1† Anthony nthony E. Kincaid, 2 Richard A. Bessen, 3 and Jason C. Bartz Bartz4*
Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison 53706 537061; Department of
Physical Therapy Therapy2 and Department of Medical Microbiology and Immunology, 4 Creighton University, Omaha,
Nebraska 68178; and Department of Veterinary Molecular Biology, Montana
State University, Bozeman, Montana 59718 597183
Received 3 May 2005/Accepted 10 August 2005
Chronic wasting disease (CWD) is an emerging prion disease of deer and elk. The risk of CWD transmission
to humans following exposure to CWD-infected tissues is unknown. To assess the susceptibility of nonhuman
primates to CWD, two squirrel monkeys were inoculated with brain tissue from a CWD-infected mule deer. The
CWD-inoculated squirrel monkeys developed a progressive neurodegenerative disease and were euthanized at
31 and 34 months postinfection. Brain tissue from the CWD-infected squirrel monkeys contained the abnormal
isoform of the prion protein, PrP-res, and displayed spongiform degeneration. This is the first reported
transmission of CWD to primates.
Chronic wasting disease (CWD) is a prion disease of elk and
deer in North America that was first identified at cervid re- research
search facilities in Colorado and Wyoming in the late 1960s
(17, 18). CWD has been identified on cervid game farms from
Montana to New York and has been diagnosed in wild deer
and elk in Colorado, Wyoming, Nebraska, South Dakota, Wis- Wisconsin,
consin, New Mexico, Illinois, and Utah and in Saskatchewan,
Canada (1, 14, 15). The geographic distribution of CWD in
deer and elk has been expanding and will likely result in an
increase in human exposure to the CWD agent. Although
there have been no cases of human prion disease linked to
CWD infection, the risk of interspecies transmission of CWD
to humans following consumption of CWD-infected tissues is
uncertain (5, 13).
One approach to assess the susceptibility of humans to an- animal
imal prion diseases is by experimental transmission to nonhu- nonhuman
man primates (9–11). To investigate the susceptibility of non- nonhuman
human primates to CWD, two adult female squirrel monkeys
(Saimiri sciureus sciureus) were intracerebrally (i.c.) inoculated with 200
"l of a 20% (wt/vol) brain homogenate from a female mule
deer in the clinical phase of CWD (inoculum was a gift from
Elizabeth Williams, Department of Veterinary Sciences, Uni- University
versity of Wyoming, Laramie, WY). Both CWD-inoculated
squirrel monkeys developed a progressive neurological disease
and were euthanized at the terminal stages of disease at 31 and
34 months postinfection, respectively (data on clinical symp- symptoms
toms and the time to onset of disease were not available).
To determine whether the abnormal form of the prion pro- protein,
tein, PrP-res, was present in the CWD-infected squirrel mon- monkeys,
keys, brain homogenates were analyzed by Western blotting as
previously described using the anti-PrP monoclonal antibody
6H4 (Prionics AG, Switzerland) (2). For this analysis, a 5%
(wt/vol) brain homogenate in Dulbecco’s phosphate-buf buffered fered
saline (Mediatech, Inc.) from CWD-infected squirrel monkeys,
a CWD-infected elk, or an uninfected mouse was either di- digested
gested with proteinase K (PK) (4 U/ml; United States Bio- Biochemical)
chemical) fo for 1 h a r at 37°C with agitation or was not digested
with PK. In the samples that were not digested with PK, PrP
migrated between 21 and 35 kDa in the CWD-infected squirrel
monkeys (Fig. 1, lanes 1 and 2) and between 30 and 35 kDa in
the CWD-infected elk (Fig. 1, lane 3) and in the uninfected
mouse sample (Fig. 1, lane 4). In the samples that were di- digested
gested with PK, PrP-res were detected in the two CWD-in- infected
fected squirrel monkeys (Fig. 1, lanes 5 and 6) and in the
CWD-infected elk sample (Fig. 1, lane 7). In the PK-digested
uninfected mouse brain, PrP was not detected (Fig. 1, lane 8),
indicating that PK digestion completely removed the PK-sen- sensitive
sitive isoform of PrP. In both CWD-infected squirrel monkeys,
the migration of the three PrP-res polypeptides on sodium
dodecyl sulfate-polyacrylamide gels was similar. The diglyco- diglycosylated
sylated PrP-res polypeptide migrated at 30 kDa similar to what
has been reported for squirrel monkeys infected with sporadic
Creutzfeldt-Jakob disease (CJD), kuru, and scrapie (4). The
relative abundance of PrP-res in the brain from the squirrel
monkey that was sacrificed at 34 months postinfection (Fig. 1,
lane 5) was greater than that in the squirrel monkey sacrificed
at 31 months postinfection (Fig. 1, lane 6) and may represent
dif differences ferences in the state of disease progression when the animals
were sacrificed.
Histological examination of the brain, brain stem, and spinal
cord from the squirrel monkey that was euthanized at 31
months postinfection revealed widespread spongiform changes
that are consistent with CWD-induced neurodegeneration.
* Corresponding author. Mailing address: Department of Medical
Microbiology and Immunology, Creighton University, 2500 California
Plaza, Omaha, NE 68178. Phone: (402) 280-1811. Fax: (402) 280-1875.
† Deceased.
Spongiform lesions in the neuropil were predominantly located
in subcortical gray matter structures of the forebrain. There
was widespread spongiform change in the putamen, caudate
nucleus, nucleus accumbens, lateral and medial hypothalamus,
hippocampal formation (CA 1), amygdala, and dorsomedial
thalamus (Fig. 2). Dif Diffuse fuse spongiosis was found in the interpe- interpeduncular
duncular nucleus and substantia nigra in the midbrain and in
the reticular formation of the pons and medulla. Due to the
limited number of histological sections, a detailed comparison
of the neuropathology in CWD-infected squirrel monkeys and
other prion transmission studies in squirrel monkeys was not
The time to terminal disease following inoculation of squir- squirrel
rel monkeys with the CWD agent, 31 and 34 months, was
longer than for squirrel monkeys that were i.c. inoculated with
transmissible mink encephalopathy agent (9 to 12 months) and
scrapie agent (16 months) but is within the reported range of
the time to terminal disease following i.c. inoculation with
sporadic CJD (11 to 37 months) and kuru (10 to 48 months) (6,
8). This variation in disease progression following experimen- experimental
tal transmission of sporadic CJD, kuru, and CWD to squirrel
monkeys could be due to dif differences ferences in the inoculation dose,
strain of the prion agent, or the ability to establish infection
upon interspecies transmission. Regardless, this study illus- illustrates
trates that a nonhuman primate can develop a prion disease
following i.c. inoculation with a brain homogenate from a
CWD-infected mule deer.
Direct comparison of the ability of the CWD agent to cause
disease in squirrel monkeys following experimental i.c. inocu- inoculation
lation and the susceptibility of humans to CWD infection must
be interpreted with caution. Although squirrel monkeys are
susceptible to experimental infection with kuru and CJD, they
are also susceptible to experimental infection with scrapie (8),
and there is no epidemiological evidence to suggest that
scrapie can be transmitted to humans (16). These data suggest,
following direct cerebral inoculation, squirrel monkeys may
not be a good experimental model for assessing human sus- susceptibility
ceptibility to animal prion diseases. Oral exposure is the likely
natural route of human exposure to CWD, and in experimental
animals, this route is much less ef efficient ficient at causing disease than
i.c. inoculation (3, 7, 12). Therefore, the ability of scrapie and
CWD to cause disease in primates by oral infection needs to be
established to further resolve the issue of susceptibility of hu- humans
mans to CWD infection.
Richard Marsh, who performed the experimental transmission of
CWD to squirrel monkeys, died in 1997 before these experiments were
completed. Due to the emergence of CWD in deer and elk and the
potential risk for CWD transmission to humans, we present his find- findings
ings with additional tissue analysis.
We thank Al Jenny, USDA-APHIS-VS-NVSL for the gift of the
CWD-infected elk tissue.
We dedicate the manuscript to Elizabeth Williams for her pioneer- pioneering
ing work on CWD.
1. Animal and Plant Health Inspection Services, Marketing and Regulatory
Programs, U.S. Department of Agriculture. 2005. [Online.] http://www.aphis
FIG. 1. Deposition of the abnormal isoform of the prion protein,
PrP-res, in the brain of squirrel monkeys inoculated with chronic
wasting disease. Western blot analysis of 250- "g tissue equivalents of
brain homogenates digested with proteinase K or not digested with
proteinase K was performed. The brain homogenates were from a
CWD-infected squirrel monkey that was sacrificed at 34 months (lanes
1 and 5) or at 31 months postinfection (lanes 2 and 6), a CWD-infected
elk (lanes 3 and 7), and an uninfected mouse (lanes 4 and 8). The
arrow indicates the location of the 29-kDa molecular mass marker.
FIG. 2. Spongiform degeneration in brain tissue from a squirrel
monkey inoculated with chronic wasting disease and euthanized at 31
months postinfection. (A) Low-power view of the lentiform nucleus,
showing the distribution of spongiform changes in the putamen (Pu)
and lack of spongiosis in the globus pallidus (Gp). Ac, anterior com- commissure.
missure. (B) High-power view of the area outlined in panel A that
exhibits widespread spongiosis. Bars # 100 microns.
VOL OL. 79, 2005 NOTES 13795
2. Bartz, J. C., J. M. Aiken, and R. A. Bessen. 2004. Delay in onset of prion
disease for the HY strain of transmissible mink encephalopathy as a result of
prior peripheral inoculation with the replication-deficient DY strain. J. Gen.
Virol. 85: 265–273.
3. Bartz, J. C., A. E. Kincaid, and R. A. Bessen. 2003. Rapid prion neuroinva- neuroinvasion
sion following tongue infection. J. Virol. 77: 583–591.
4. Beekes, M., E. Baldauf, S. Cassens, H. Diringer, P. Keyes, A. C. Scott, G. A.
Wells, P. Brown, C. J. Gibbs, Jr., and D. C. Gajdusek. 1995. Western blot
mapping of disease-specific amyloid in various animal species and humans
with transmissible spongiform encephalopathies using a high-yield purifica- purification
tion method. J. Gen. Virol. 76: 2567–2576.
5. Belay, E. D., P. Gambetti, L. B. Schonberger, P. Parchi, D. R. Lyon, S.
Capellari, J. H. McQuiston, K. Bradley, G. Dowdle, J. M. Crutcher, and
C. R. Nichols. 2001. Creutzfeldt-Jakob disease in unusually young patients
who consumed venison. Arch. Neurol. 58: 1673–1678.
6. Brown, P., C. J. Gibbs, Jr., P. Rodgers-Johnson, D. M. Asher, M. P. Sulima,
A. Bacote, L. G. Goldfarb, and D. C. Gajdusek. 1994. Human spongiform
encephalopathy: the National Institutes of Health series of 300 cases of
experimentally transmitted disease. Ann. Neurol. 35: 513–529.
7. Diringer, H., J. Roehmel, and M. Beekes. 1998. Ef Effect fect of repeated oral
infection of hamsters with scrapie. J. Gen. Virol. 79: 609–612.
8. Gibbs, C. J., Jr., and D. C. Gajdusek. 1973. Experimental subacute spongi- spongiform
form virus encephalopathies in primates and other laboratory animals. Sci- Science
ence 182: 67–68.
9. Gibbs, C. J., Jr., and D. C. Gajdusek. 1972. Transmission of scrapie to the
cynomolgus monkey (Macaca fascicularis). Nature 236: 73–74.
10. Lasmezas, C. I., J. P. Deslys, R. Demaimay, K. T. Adjou, F. Lamoury, D.
Dormont, O. Robain, J. Ironside, and J. J. Hauw. 1996. BSE transmission to
macaques. Nature 381: 743–744.
11. Lasmezas, C. I., J. G. Fournier, V. Nouvel, H. Boe, D. Marce, F. Lamoury, N.
Kopp, J. J. Hauw, J. Ironside, M. Bruce, D. Dormont, and J. P. Deslys. 2001.
Adaptation of the bovine spongiform encephalopathy agent to primates and
comparison with Creutzfeldt-Jakob disease: implications for human health.
Proc. Natl. Acad. Sci. USA 98: 4142–4147.
12. Prusiner, S. B., S. P. Cochran, and M. P. Alpers. 1985. Transmission of
scrapie in hamsters. J. Infect. Dis. 152: 971–978.
13. Raymond, G. J., A. Bossers, L. D. Raymond, K. I. O’Rourke, L. E. McHol- McHolland,
land, P. K. Bryant, M. W. Miller, E. S. Williams, M. Smits, and B. Caughey.
2000. Evidence of a molecular barrier limiting susceptibility of humans,
cattle and sheep to chronic wasting disease. EMBO J. 19: 4425–4430.
14. Sigurdson, C. J., and M. W. Miller. 2003. Other animal prion diseases. Br.
Med. Bull. 66: 199–212.
15. Spraker, T. R., M. W. Miller, E. S. Williams, D. M. Getzy, W. J. Adrian,
G. G. Schoonveld, R. A. Spowart, K. I. O’Rourke, J. M. Miller, and P. A.
Merz. 1997. Spongiform encephalopathy in free-ranging mule deer
(Odocoileus hemionus), white-tailed deer (Odocoileus virginianus) and
Rocky Mountain elk (Cervus elaphus nelsoni) in northcentral Colorado.
J. Wildl. Dis. 33: 1–6.
16. van Duijn, C. M., N. Delasnerie-Laupretre, C. Masullo, I. Zerr, R. de Silva,
D. P. Wientjens, J. P. Brandel, T. Weber, V. Bonavita, M. Zeidler, A. Alp- Alperovitch,
erovitch, S. Poser, E. Granieri, A. Hofman, R. G. Will, and European Union
(EU) Collaborative Study Group of Creutzfeldt-Jakob disease (CJD). 1998.
Case-control study of risk factors of Creutzfeldt-Jakob disease in Europe
during 1993–95. Lancet 351: 1081–1085.
17. Williams, E. S., and S. Young. 1980. Chronic wasting disease of captive mule
deer: a spongiform encephalopathy. J Wildl. Dis. 16: 89–98.
18. Williams, E. S., and S. Young. 1982. Spongiform encephalopathy of Rocky
Mountain elk. J. Wildl. Dis. 18: 465–471.

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