Mutation and Selection of Prions 英文参考文献.docVIP

Pearls MutationandSelectionofPrions CharlesWeissmann* DepartmentofInfectology,ScrippsFlorida,Jupiter,Florida,UnitedStatesofAmerica PrionDiseases PrP gene. Many ‘‘classical’’ strains currently propagated in mice and hamsters, such as 79A, 22L, and ME7, originated from scrapie-infected sheep or goats [7] and were cloned by endpoint dilutioninmice. Prion diseases, or transmissible spongiform encephalopathies (TSEs), occur naturally in several species, including humans, cattle,sheep,anddeer,andcanbetransmittedexperimentallyto many others. Typically, incubation times are relatively long, extending to 40 years or more in humans; however, after appearanceofclinicalsymptoms,deathmostlyensueswithinless thanayear,asaconsequenceofneurodegenerationaccompanied byaccumulationofabnormalconformersofthehostproteinPrP. Natural transmission usually occurs perorally, as exemplified by thekuruepidemicamongtheForepeopleofPapuaNewGuinea, attributed to cannibalistic practices; the bovine spongiform encephalopathy (BSE) epizootic in the United Kingdom at the endoflastcentury,causedbyfeedingofcontaminatedmeat-and- bone meal to cattle; or the current epizootic of chronic wasting disease afflicting cervids in 19 states of the United States. Transmission of BSE prions to young humans gave rise to a limited outbreak of a novel illness, variant Creutzfeldt-Jakob disease (vCJD), almost exclusively in the UK. Sporadic cases of prion disease occur at very low frequency in human populations (sCJD) and in cattle herds (atypical BSE), and are attributed to spontaneous generation of prions in the affected individuals. Finally, familial forms of human prion disease are linked to a variety of different, dominant mutations in the PRNP gene, and whileafflictedfamiliesarerare,penetranceisveryhigh. Strain-specific properties of the prion are believed to be enciphered in the conformation of the cognate PrPSc [8], and indeed, distinct strains are often associated with PrPSc species differing in physicoch