Prion particle (prion), also known as prion, is caused by human and animal transmissible spongiform encephalopathies occurred (transmissible spongiform encephalopathy, tse) of the pathogen, belongs to a special kind of infectious protein particles. In recent years, associated with bovine spongiform encephalopathy (bovine spongiform encephalo pathy, bse) a serious epidemic in the UK, and has proved to bse pathogenic factors can be transmitted to humans and cause a new variant g - Jakob disease, a high degree of concern for the countries in the world . The main components of prion particles protease resistant protein (proteinaseresistantprotein, prp), does not contain nucleic acid. Able to replicate without nucleic acid, which is a number of biological scientists, a mystery.
First, the biological characteristics
Virus-free structure of prion particles, can be 5nm or smaller filtration membrane, formaldehyde, ethanol, protease, heating (80 ℃), ionizing radiation and strong resistance to UV, while the phenols, ether, acetone, sensitive to strong detergents and bleach. Purification of brain tissue from infected animals, prion particles, is a resistance to protease digestion of the protein polymer, molecular weight of 27000 to 30000, it is also known prp27-30, Department of hydrophobic glycoprotein. The cause of scrapie infected hamster brain child separation prp called the prpsc (scrapieisoformofprp). Normal human and animal neural cells can express a prp analogues, known as precursors or prion particles prp precursor molecules, that prpc (cellularisoformofprp) or prp33-35 (because of its molecular weight of 33,000 ~ 35,000). prpc distributed in the surface of normal cells, protease sensitive, and its function is unclear. prpsc and prpc of a similar structure, but tertiary structure determined by the conformational differences (Figure 35-1). prpsc three-dimensional conformation with four β-sheet and two α-helical structure; and prpc almost no β-sheet with four α-helical structure. The main difference between the conformation of the 2 for the prpc and prpsc α-helix structure of four β-sheet changes, and speculated that the original non-toxic prpc can change this structure to obtain toxicity and protease resistance. Under normal circumstances, prpc degraded rapidly after synthesis, which changes the incentive structure for the prpsc unknown, may be prpc Department prpsc binding to cell surface due to the trigger.
Genes in human prpc 20 short arm of chromosome, gene length of 759kb, including an exon and an open reading frame (orf), no introns, encoding 253 amino acids. Studies have shown that people prpc No. 102,178,198,200 bit gene mutation, and genetic grams - the occurrence of related Jakob disease.
Second, pathogenicity and immunity
prpsc proliferation mechanism is unclear. Presumably, prpsc prpc combination with the cell surface, which can trigger the formation of more allosteric prpsc, a large number of prpsc release from the cells aggregate in the brain to form amyloid plaques particular, further development of spongiform encephalopathy. Particles are known to cause human and animal prion diseases are: kuru disease (tremor disease), g - Jakob disease and its variants (variantcjd, vcjd), cerstmann-straussler syndrome, scrapie (scrapieofsheepandgoat), BSE (madcowdisease) also known as bovine spongiform encephalopathy (bovinespongiformencephalopathy, bse), infectious ferret leukoencephalopathy (transmissibleminkencephalopathy) and large mule deer CWD (chronicwastingdiseaseofmuledeer) and so on. Common characteristic of these diseases are: a long incubation period, the lesion occurs only in the central nervous system, rather than involving other organs; pathology is degeneration of neurons, degeneration, amyloid plaque formation, such as stellate cell proliferation , the formation of spongiform encephalopathy or leukoencephalopathy; lesions without inflammatory response. Patients may have dementia, ataxia, nystagmus and clinical manifestations of epilepsy, no specific immune response to prion particles. In this section, the common people spongiform encephalopathy (g - Jakob disease and kuru disease) are described below.
(A) g - Jakob disease
G - Jakob disease in the long incubation period, up to several decades. Initial clinical symptoms in terms of spirit and feeling, then appear ataxia, and further development of muscle cramps and accompanied by dementia, the course most of the 5 to 12 months, 4 to 5 years older, eventually leading to death. Age of on_set_ more than 50 years of age. Grain infection by prion disease brain tissue, white blood cells, or certain organs of the culture transmitted to primates, mice and guinea pigs. Has been found in brain tissue showed a high level of infection per gram of brain tissue of up to 107.
It is noteworthy that the British discovered in 1996 grams - a new variant of Jakob disease, occurs in young people, and the clinical symptoms and pathological changes were associated with the traditional g - Jakob disease is different. Disease involving the United Kingdom and other European countries. Bovine prion is due to consumption of contaminated meat and bone meal tablets caused. In 1996 alone, in the UK and France appeared more than 20 cases of new variant g - Jakob disease (newvariantcjd, vcjd). Study, vcjd naturally occurring or experimentally infected with bse abnormal accumulation of the protein appears with the same type of glycosylation, mice inoculated with the same after the neuropathological damage. vcjd specificity of transmission is unclear, but the pollution is nerve tissue or beef products from cattle most likely.
(B) kuru
Pathological changes occurred in the central nervous system, associated with diffuse degeneration of neurons or ganglia and cerebral cortex of cavernous transformation. The disease does not show inflammation.
Third, microbiology test method
Microbiological pathogens during the examination can be taken and diseased brain tissue in patients with cerebrospinal fluid, etc., through staining, immunohistochemistry and Western blot used to detect prpsc. In the diseased materials shall prevent accidental transmission. Microbiological examination methods include: ① the electron microscopy: particles can be observed with the infectious prion disease-related pathology. ② neuropathological examination: a sponge-like lesions seen sparsely distributed throughout the cerebral cortex, neurons disappeared, stellate cell proliferation, confluent lesions typical of spongiform vacuoles, surrounded by a large number of amyloid plaques fast, clear stained with he and the pas visible. ③ specific immunological method is simple, specific marker for prion infection prpsc particle detection, the patient brain tissue by protease digestion to remove normal cells prpc, through the dot immunogold (dotblotmethod) or Western blot detection prpsc. Get lesion or nerve tissue cells in peripheral blood leukocytes; fluorescent antibody staining can also be used for positioning of the prion particle. ④ prp gene detection: Determination of the short arm of chromosome No. 20 of the prp gene sequences can diagnose genetic diseases infectious prion particles. Pcr amplified using whole genome prpc by site-specific oligonucleotide probe hybridization, mutation screening, and then sequenced to identify mutations prpc sites. ⑤ prion particle separation: inoculation of susceptible animals with prion particles can produce the typical spongiform encephalopathy, with a diagnosis, but took too long and costs too much. Mice transferred prpc sensitive to human prion particles, the susceptibility of squirrel monkeys on cjd most stable. In the above in many ways, is still pathological diagnosis of prion particles as a common means of infection.
Fourth, the principle of prevention
Currently, infectious diseases, prion particles there is no effective treatment. Only with direct contact with the hospital infection-related brain tissue, to eliminate the diagnosis of dementia patients for dialysis positioning cross-use of neurosurgical devices, so as to avoid the spread of these diseases. When making organ transplant should not be _select_ed neurological diseases not yet diagnosed patients as donors. Recombinant human growth factors already on the market, can be used when necessary to replace human pituitary growth factor prepared to reduce the iatrogenic transmission. In case of potentially infectious material, available 5% sodium hypochlorite solution for 1 hour, or 134 ℃ 1 小时 autoclaving. |
|
|