Prions infectivity

Other animal prion diseases. Outbreaks of transmissible mink encephalopathy and chronic wasting disease in captive populations of mink, mule deer and elk in certain regions of the U.S.A. have also been attributed to prion-infected foodstuffs, although the origin of prion infection is unclear [8], Epidemiological studies suggest lateral transmission as the most plausible explanation for the spread of chronic wasting disease in captive populations... 

Peripheral pathogenesis involves the lymphoreticular system. Although the pathological consequences of prion infection occur in the central nervous system, and experimental transmission of these diseases is most efficiently accomplished by intracerebral inoculation, most natural infections do not occur by these means. Indeed, administration to sites other than the central nervous system is known to be associated with much longer incubation periods, which may extend to 20 years or more [5,12]. Experimental evidence suggests that this latent period is associated with clinically silent prion replication in... 

Subclinical or carrier states of prion disease have major implications for public health, most notably iatrogenic transmission from apparently healthy individuals. The existence of subclinical prion infections also raise the possibility that other species (such as sheep, pigs and poultry), exposed to BSE prions by contaminated feed, might be able to develop subclinical carrier states. Given that BSE prions are pathogenic in a wide variety of species, and that the strain characteristics of BSE prions are retained upon transmission to new species, it must be considered possible, if not probable, that BSE in animals other than cattle will retain pathogenicity for humans. 

Hill, A. F. and Collinge, J. Subclinical prion infection. Trends Microbiol. 11 578-584, 2003. 

Mallucci, G. et al. Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science 302 871-874, 2003. 

With Ure2p, the N-terminal 65 amino acids can induce prion formation and yeast cells expressing only Ure2p66-354 are immune to prion infection (Masison and Wickner, 1995). On the other hand, a yeast strain expressing only Ure2p1-65 can also maintain [URE3] for many generations and after that pass it on to another strain (Masison et al., 1997). 

To account for the species barrier of prion infectivity, it was proposed that the 109-112 epitope recognized by antibody 3F4 is localized at the... 

Foetal mesencephalic tissue has been implanted in the striatum of patients with the juvenile form of Parkinson s disease and has been shown to develop functional axons this has enabled the dose of L-dopa to be reduced. Both imaging and pharmacological studies have now shown that functional dopaminergic neurons can develop in the brain of the patient following tissue transplantation. However, a major ethical objection has been raised to such transplants as six to seven foetal brains are required to obtain sufficient tissue. In addition, only about 20% of neurons survive transplantation. The ethical problem may be overcome by using brain transplants from domestic animals such as pigs. Such xenotransplants have been shown to survive in the human brain but the main problem with the extensive use of such transplants is the possible spread of viruses and prion infections. 

Kneipp, J., L.M. Miller, M. Joncic, M. Kittel, P. Lasch, M. Beekes, and D. Naumann. 2003. In situ identification of protein stmctural changes in prion-infected tissue. Bioch. Biophys. Acta 1639 152-158. 

In 2001, the antimalarial drug quinacrine and the antipsychotic drug chlorpro-mazine (Fig. 1.14) were shown to inhibit prion infection in cells. Pmsiner and coworkers [24] identified the drugs independently, and found that they inhibited the conversion of normal prion protein into infectious prions, and also cleared prions from infected cells. Both drugs can cross over from the bloodstream to the brain, where the prion diseases are localized. 

Fig. 1.14 Old drugs, new use. The antimalarial drug quinacrine and the antipsychotic drug chlorpromazine are able to inhibit prion infection [24].

The acquired prion diseases account for less than 1 % of all human prion disease cases and these include variant CJD, iatrogenic CJD (iCJD), and kum (reviewed by Will, 2003). In these cases, prion infection is either orally acquired or associated vdth accidental transmission via medical practices. Many of these latter cases involve contamination with brain tissue, which contains the highest amount of prion infectivity, from the donor host. 

Iatrogenic CJD is the second most common acquired human prion disease and these cases are the result of accidental infection due to contact with prion contaminated tissues or instruments during medical procedures (Table 29.1). The mode of prion infection include surgical equipment (e.g., surgical insd uments, depth electrodes), transplantation of human tissues (comeal, dura mater), intramuscular injections with growth hormone or gonadotrophin extracted from human pituitary tissues, or blood transfusion (reviewed by Will, 2003). The most likely source of infection is from donors with subclinical sCJD, except for the tw o transfusion-related cases that have been linked to blood donors who developed vCJD several years later (reviewed by Ironside, 2006). The incubation period in these transfusion related cases was 5 to 6 years, v hich is shorter than primary vCJD infection in humans. 

The immune system plays a central role in the pathogenesis of prion infection. In the acquired human prion diseases, it is the initial site of agent replication prior to entry into the nervous system but the immune system does not appear to be essential in the pathogenesis of the familial and sporadic human prion diseases. Followdng peripheral exposure to the prion agent, the immune system can amplify prion infection but, interestingly, the adaptive immune response does not play a role in the clearance of the prion agent. 

In sheep wdth mastitis, a chronic inflammation of the mammary gland, and concurrent scrapie, prion infection is present in FDCs and macrophages in lymphoid follicles that develop adjacent to mammary ducts (Ligios et ah, 2005). Although, there are no accounts of prion shedding from colostrum in scrapie-infected sheep without mastitis, macrophages can be shed into the milk of sheep with mastitis. Secretion of the scrapie-infected macrophages in colostrum of sheep with mastitis could potentially play a role in vertical transmission of scrapie since the route of spread from ewe to lamb has not been determined. 

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