PrpTSE distribution in a primate model of variant, sporadic, and iatrogenic Creutzfeldt-Jakob disease

被引:59
作者
Herzog, C [1 ]
Rivière, J [1 ]
Lescoutra-Etchegaray, N [1 ]
Charbonnier, A [1 ]
Leblanc, V [1 ]
Salès, S [1 ]
Deslys, JP [1 ]
Lasmézas, CI [1 ]
机构
[1] Commissariat Energie Atom, Dept Rech Med, F-92265 Fontenay Aux Roses, France
关键词
D O I
10.1128/JVI.79.22.14339-14345.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Human prion diseases, such as Creutzfeldt-jakob disease (CJD), are neurodegenerative and fatal. Sporadic CjD (sCJD) can be transmitted between humans through medical procedures involving highly infected organs, such as the central nervous system. However, in variant CjD (vCJD), which is due to human contamination with the bovine spongiform encephalopathy (BSE) agent, lymphoreticular tissue also harbors the transmissible spongiform encephalopathy-associated prion protein (Prp(TSE)), which poses a particularly acute risk for iatrogenic transmission. Two blood transfusion-related cases are already documented. In addition, the recent observation of PrpTSE in spleen and muscle in sCJD raised the possibility that peripheral PrPTSE is not limited to vCJD cases. We aimed to clarify the peripheral pathogenesis of human TSEs by using a nonhuman primate model which mimics human diseases. A highly sensitive enzyme-linked immunosorbent assay was adapted to the detection of extraneural Prp(TSE). We show that affected organs can be divided into two groups. The first is peripheral organs accumulating large amounts of Prp(TSE), which represent a high risk of iatrogenic transmission. This category comprises only lymphoreticular organs in the vCJD/BSE model. The second is organs with small amounts of PrPTSE associated with nervous structures. These are the muscles, adrenal glands, and enteric nervous system in the sporadic, iatrogenic, and variant CJD models. In contrast to the first set of organs, this low level of tissue contamination is not strain restricted and seems to be linked to secondary centrifugal spread of the agent through nerves. It might represent a risk for iatrogenic transmission, formerly underestimated despite previous reports of low rates of transmission from peripheral organs of humans to nonhuman primates (5, 10). This study provides an additional experimental basis for the classification of human organs into different risk categories and a rational re-evaluation of current risk management measures.
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页码:14339 / 14345
页数:7
相关论文
共 32 条
  • [1] PrPSc accumulation in myocytes from sheep incubating natural scrapie
    Andréoletti, O
    Simon, S
    Lacroux, C
    Morel, N
    Tabouret, G
    Chabert, A
    Lugan, S
    Corbière, F
    Ferré, P
    Foucras, G
    Laude, H
    Eychenne, F
    Grassi, J
    Schelcher, F
    [J]. NATURE MEDICINE, 2004, 10 (06) : 591 - 593
  • [2] BASRTZ JC, 2003, J VIROL, V77, P583
  • [3] Prions in skeletal muscle
    Bosque, PJ
    Ryou, C
    Telling, G
    Peretz, D
    Legname, G
    DeArmond, SJ
    Prusiner, SB
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (06) : 3812 - 3817
  • [4] Creutzfeldt-Jakob disease: implications for gastroenterology
    Bramble, MG
    Ironside, JW
    [J]. GUT, 2002, 50 (06) : 888 - 890
  • [5] HUMAN SPONGIFORM ENCEPHALOPATHY - THE NATIONAL-INSTITUTES-OF-HEALTH SERIES OF 300 CASES OF EXPERIMENTALLY TRANSMITTED DISEASE
    BROWN, P
    GIBBS, CJ
    RODGERSJOHNSON, P
    ASHER, DM
    SULIMA, MP
    BACOTE, A
    GOLDFARB, LG
    GAJDUSEK, DC
    [J]. ANNALS OF NEUROLOGY, 1994, 35 (05) : 513 - 529
  • [6] The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy
    Brown, P
    Rohwer, RG
    Dunstan, BC
    MacAuley, C
    Gajdusek, DC
    Drohan, WN
    [J]. TRANSFUSION, 1998, 38 (09) : 810 - 816
  • [7] BRUCE M, 1996, 3 INT S TRANSM SUB S
  • [8] Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent
    Bruce, ME
    Will, RG
    Ironside, JW
    McConnell, I
    Drummond, D
    Suttie, A
    McCardle, L
    Chree, A
    Hope, J
    Birkett, C
    Cousens, S
    Fraser, H
    Bostock, CJ
    [J]. NATURE, 1997, 389 (6650) : 498 - 501
  • [9] TRANSMISSION OF 2 SUBACUTE SPONGIFORM ENCEPHALOPATHIES OF MAN (KURU AND CREUTZFELDT-JAKOB DISEASE) TO NEW WORLD MONKEYS
    GAJDUSEK, DC
    GIBBS, CJ
    [J]. NATURE, 1971, 230 (5296) : 588 - &
  • [10] PRECAUTIONS IN MEDICAL-CARE OF, AND IN HANDLING MATERIALS FROM, PATIENTS WITH TRANSMISSIBLE VIRUS DEMENTIA (CREUTZFELDT-JAKOB-DISEASE)
    GAJDUSEK, DC
    GIBBS, CJ
    ASHER, DM
    BROWN, P
    DIWAN, A
    HOFFMAN, P
    NEMO, G
    ROHWER, R
    WHITE, L
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1977, 297 (23) : 1253 - 1258