사슴광우병(만성소모성질환, CWD) 임상 증상이 나타나지 않은 무증상 사슴(CWD-infected mule deer )이 임상증상을 나타내기 전에 분변을 통해 변형 프리온을 배출한다는 프루시너 박사(노벨생리의학상 수상자, 교신저자)팀의 연구결과가 2009년 9월 9일에 출간된
[네이처(Nature)] 온라인판에 letter 형태로 실렸습니다. 프루시너 박사팀의 연구결과는 이미 2008년 5월 27일자 [전염병학회지(The Journal of Infectious Diseases)]에 발표된 바가 있습니다.
신경증상을 나타내기 7~11개월 전에 분변을 통해 변형 프리온을 배출한 사슴 5두에게서 모은 변형 프리온 단백질을 유전자 형질전환 생쥐 15두에 뇌내 접종을 해보았더니 그 중에서 14두에서 감염성이 있는 변형 프리온이 검출되었다고 합니다.
현재까지의 과학적 연구결과에 따르면, 사슴광우병(만성소모성질환, CWD)이 인간에게 전염된다는 과학적 증거는 없는 상태입니다. 다만 실험관 내 연구에서 사슴의 변형프리온 단백질이 인간의 정상 프리온 단백질을 변형시켰다는 연구결과만 발표되었고, 동물실험에서는 이러한 결과가 재현되지 않은 바 있습니다.
사슴은 침을 통해서도 변형 프리온 단백질을 배출하기 때문에 분변을 통해서 변형 프리온을 배출한다는 이번 연구결과는 사슴광우병(만성소모성질환, CWD)을 근절시키기가 아주 어려울 것이라는 점을 시사합니다.
Letter
출처 : Nature advance online publication 9 September 2009 | doi:10.1038/nature08289; Received 11 May 2009; Accepted 16 July 2009; Published online 9 September 2009
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature08289.html
Asymptomatic deer excrete infectious prions in faeces
Gültekin Tamgüney1,2, Michael W. Miller3, Lisa L. Wolfe3, Tracey M. Sirochman3, David V. Glidden4, Christina Palmer1, Azucena Lemus5, Stephen J. DeArmond1,5 & Stanley B. Prusiner1,2
- Institute for Neurodegenerative Diseases,
- Department of Neurology, University of California, San Francisco, California, 94143 USA
- Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, Colorado, 80526 USA
- Department of Epidemiology and Biostatistics,
- Department of Pathology, University of California, San Francisco, California, 94143 USA
Correspondence to: Stanley B. Prusiner1,2 Correspondence and requests for materials should be addressed to S.B.P. (E-mail: Email: stanley@ind.ucsf.edu.)
Infectious prion diseases1—scrapie of sheep2 and chronic wasting disease (CWD) of several species in the deer family3, 4—are transmitted naturally within affected host populations. Although several possible sources of contagion have been identified in excretions and secretions from symptomatic animals5, 6, 7, 8, the biological importance of these sources in sustaining epidemics remains unclear. Here we show that asymptomatic CWD-infected mule deer (Odocoileus hemionus) excrete CWD prions in their faeces long before they develop clinical signs of prion disease. Intracerebral inoculation of irradiated deer faeces into transgenic mice overexpressing cervid prion protein (PrP) revealed infectivity in 14 of 15 faecal samples collected from five deer at 7–11 months before the onset of neurological disease. Although prion concentrations in deer faeces were considerably lower than in brain tissue from the same deer collected at the end of the disease, the estimated total infectious dose excreted in faeces by an infected deer over the disease course may approximate the total contained in a brain. Prolonged faecal prion excretion by infected deer provides a plausible natural mechanism that might explain the high incidence and efficient horizontal transmission of CWD within deer herds3, 4, 9, as well as prion transmission among other susceptible cervids.
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Transmission and Detection of Prions in Feces
The Journal of Infectious Diseases 2008;198:81–89 © 2008 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2008/19801-0015$15.00 DOI: 10.1086/588193
MAJOR ARTICLE
Transmission and Detection of Prions in Feces
Jiri G. Safar,1,2 Pierre Lessard,1 Gültekin Tamgüney,1,2 Yevgeniy Freyman,1 Camille Deering,1 Frederic Letessier,1 Stephen J. DeArmond,1,3 and Stanley B. Prusiner1,2,4
1Institute for Neurodegenerative Diseases, Departments of 2Neurology, 3Pathology, and 4Biochemistry and Biophysics, University of California, San Francisco, San Francisco
In chronic wasting disease (CWD) in cervids and in scrapie in sheep, prions appear to be transmitted horizontally. Oral exposure to prion-tainted blood, urine, saliva, and feces has been suggested as the mode of transmission of CWD and scrapie among herbivores susceptible to these prion diseases. To explore the transmission of prions through feces, uninoculated Syrian hamsters (SHas) were cohabitated with or exposed to the bedding of SHas orally infected with Sc237 prions. Incubation times of 140 days and a rate of prion infection of 80%-100% among exposed animals suggested transmission by feces, probably via coprophagy. We measured the disease-causing isoform of the prion protein (PrPSc) in feces by use of the conformation-dependent immunoassay, and we titrated the irradiated feces intracerebrally in transgenic mice that overexpressed SHa prion protein (SHaPrP). Fecal samples collected from infected SHas in the first 7 days after oral challenge harbored 60 ng/g PrPSc and prion titers of 106.6 ID50/g. Excretion of infectious prions continued at lower levels throughout the asymptomatic phase of the incubation period, most likely by the shedding of prions from infected Peyer patches. Our findings suggest that horizontal transmission of disease among herbivores may occur through the consumption of feces or foodstuff tainted with prions from feces of CWD-infected cervids and scrapie-infected sheep.
Received 9 October 2007; accepted 15 November 2007; electronically published 27 May 2008.
(See the editorial commentary by Bosque and Tyler, on pages 8-9.)
Potential conflicts of interest: none reported.
Financial support: National Institutes of Health (grants AG02132, AG010770, NS22786, and NS14069); G. Harold and Leila Y. Mathers Foundation; Sherman Fairchild Foundation.
Reprints or correspondence: Dr. Stanley B. Prusiner, 513 Parnassus Ave., HSE-774, San Francisco, CA 94143-0518 (stanley@ind.ucsf.edu).
http://www.journals.uchicago.edu/doi/abs/10.1086/588193
The Journal of Infectious Diseases 2008;198:8–9 © 2008 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2008/19801-0004$15.00 DOI: 10.1086/588194 EDITORIAL COMMENTARY Prions’ Travels-Feces and Transmission of Prion Diseases P. J. Bosque1,4 and K. L. Tyler1,2,3,5
Departments of 1Neurology, 2Medicine, and 3Microbiology, University of Colorado Health Sciences Center, 4Department of Medicine (Neurology), Denver Health Medical Center, and 5Neurology Service, Denver Veterans Affairs Medical Center, Denver, Colorado
Received 9 January 2008; accepted 9 January 2008; electronically published 27 May 2008.
(See the article by Safar et al., on pages 81-9.)
Potential conflicts of interest: The authors report that they have no conflicts of interest regarding prions and prion disease.
Reprints or correspondence: Dr. K. L. Tyler, Neurology B-182, University of Colorado Health Sciences Center, 4200 East 9th Ave., Denver, CO 80262 (ken.tyler@uchsc.edu).
http://www.journals.uchicago.edu/doi/abs/10.1086/588194
