The Generative Brain

Kong Q et al. 2008, Evaluation of the human transmission risk of an atypical bovine spongiform encephalopathy prion strain (J Virol 82:3697-3701, PMID 18234793)

A short 2008 Journal of Virology paper from Case Western Reserve University pathology in Cleveland with the Turin veterinary reference centre and the Verona neurology group, testing whether the atypical BSE form called BASE, or L-type BSE, can cross into a human prion protein model. Brain material from two Italian BASE cattle was inoculated into transgenic mice that carry human PrP with methionine at codon 129 at about normal levels; 18 of 30 mice became infected after roughly 20 to 22 months, and protease-resistant prion protein was found in the spleens of 4 of them. The authors read this as a higher transmission rate than has been reported for classical BSE in comparable mouse models, and as a sign that BASE prions reach lymphoid tissue, while still describing a significant barrier to people who are methionine homozygous at codon 129. It is a mouse study about cattle prions and says nothing about any individual's risk. Information only, not medical or veterinary advice.

Key facts

  • Twenty-two authors are listed, first author Qingzhong Kong and last author Pierluigi Gambetti, with affiliations at the Department of Pathology, Case Western Reserve University, Cleveland; the national reference centre at the Istituto Zooprofilattico Sperimentale in Turin; and the Department of Neurological and Visual Sciences, University of Verona.
  • The paper was received on 30 November 2007, accepted on 16 January 2008, published ahead of print on 30 January 2008, and printed in the April 2008 issue, volume 82, issue 7, pages 3697 to 3701.
  • The mouse line was Tg40, which expresses human PrP with methionine at codon 129 at about wild type level on a mouse PrP knockout background.
  • Inocula came from two BASE cattle: 9 of 15 mice were infected by the first isolate with a mean incubation of 649 days and 9 of 15 by the second with a mean of 595 days, that is 18 of 30 or 60 percent at roughly 20 to 22 months.
  • Human sporadic CJD controls in the same line were reported as fully transmitting at about 9 months, with 9 affected mice per group, a mean of 263 days for sCJD MM1 and 267 days for sCJD MM2.
  • Protease-resistant PrP was found in the spleens of 4 BASE-inoculated mice, all also positive in brain, and in none of the sporadic CJD inoculated mice, which the authors took as evidence that the BASE agent is intrinsically lymphotropic.
  • Brain lesions were mild: none of 12 infected mice examined showed consistent prion type changes, two had focal ambiguous spongiform change, no amyloid plaques were seen, and histoblots put the signal mainly in thalamic, hypothalamic and brainstem nuclei.
  • The PrPres in infected mice migrated like the BASE inoculum and like sporadic CJD type 2 and about 0.29 kDa faster than classical BSE, with a glycoform ratio of about 44:39:17 against 72:20:8 for classical BSE.
  • For comparison the authors cite about 20 percent attack rate for classical BSE in the Tg650 line that overexpresses human PrP and 0 to 30 percent in other lines at one to two times normal PrP, while noting that the lines differ, so the comparison is indirect.
  • The discussion states that the barrier from BASE to people with methionine homozygosity at codon 129 is still quite significant, and calls for cattle prion surveillance to continue until the extent and origin of atypical BSE are understood.
  • Funding was United States Public Health Service grants AG014359 to Gambetti from the National Institute on Aging and NS052319 to Kong from the National Institute of Neurological Disorders and Stroke, plus an award to Gambetti from the Charles S. Britton Fund.
  • Europe PMC counted 100 citing papers on 21 October 2026; the record is free in PMC as PMC2268471.
  • A 2020 study from Madrid and Toulouse found L-type BSE transmitted to methionine 129 human PrP mice with a 100 percent attack rate, found valine 129 strongly protective even in heterozygotes, and found no H-type transmission, and it cites this paper among the earlier atypical BSE studies.

Timeline

  1. 2007Manuscript received by the Journal of Virology on 30 November.
  2. 2008Accepted on 16 January and published ahead of print on 30 January.
  3. 2008Print issue, J Virol 82(7):3697-3701.
  4. 2008The Jouy-en-Josas group reports L-type transmission to human PrP methionine 129 mice with no obvious barrier and no H-type transmission.
  5. 2016A Jouy-en-Josas paper finds no evidence that L-type BSE causes a known sporadic CJD form in human PrP mice.
  6. 2020Madrid and Toulouse report a 100 percent L-type attack rate in methionine 129 mice and a protective valine 129 effect.
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