Piero Parchi, Robert B. Petersen, Pierluigi Gambetti
{"title":"New topics in familial prion diseases","authors":"Piero Parchi, Robert B. Petersen, Pierluigi Gambetti","doi":"10.1006/smvy.1996.0023","DOIUrl":"10.1006/smvy.1996.0023","url":null,"abstract":"<div><p>Major advances have been made in the understanding of the molecular basis of phenotypic variability in human prion diseases over the last few years. Strong evidence indicates that a complex interaction between specific mutations and the polymorphic codon 129 of the prion protein gene (<em>PRNP</em>) underlies the genetic control of phenotypic expression in familial human prion diseases. Fatal familial insomnia (FFI) and a subtype of familial CJD (CJD<sup>178</sup>), two prion diseases with different clinico-pathological features, the same mutation at codon 178 of<em>PRNP</em>but a different amino acid at codon 129 of the mutant<em>PRNP</em>allele, represent the best characterized example of this complex interplay between the<em>PRNP</em>genotype and phenotypic variability. Protein studies have subsequently shown that the different genotype of the mutant allele in FFI and CJD<sup>178</sup>results in the formation of two different protease-resistant prion proteins (PrP<sup>res</sup>) which differ in size and glycosylation. These biochemical characteristics of PrP<sup>res</sup>as well as differences among distinct brain regions in the timing and rate of PrP<sup>res</sup>deposition and in the vulnerability to PrP<sup>res</sup>also appear to be major determinants of phenotypic expression in human prion diseases.</p></div>","PeriodicalId":92955,"journal":{"name":"Seminars in virology","volume":"7 3","pages":"Pages 181-187"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smvy.1996.0023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51137782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transmission of human prion diseases to rodents","authors":"Jun Tateishi","doi":"10.1006/smvy.1996.0022","DOIUrl":"10.1006/smvy.1996.0022","url":null,"abstract":"<div><p>PrP genotypes of human prion diseases were closely related to deposition types of PrP<sup>Sc</sup>, clinico-pathologic phenotypes and transmission rates to rodents. Wild type CJD with 129M/M, iatrogenic cases, and hereditary CJD with V1801, E200K, and M232R showed synaptic type deposition of PrP<sup>Sc</sup>, similar phenotypes and, except for V1801, similar transmission rates. One patient with fatal familial insomnia transmitted the disease to mice. Plaque type deposition of PrP<sup>Sc</sup>induced various phenotypes, such as GSS or Alzheimer's disease-like dementia, usually with a longer clinical course than CJD. Experimental transmission was positive from one-third of the cases with P102L but negative from other mutation cases with PrP plaques. Polymorphism at codon 129 may modify phenotypes as well as transmission rates.</p></div>","PeriodicalId":92955,"journal":{"name":"Seminars in virology","volume":"7 3","pages":"Pages 175-180"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smvy.1996.0022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51137151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reed B. Wickner, Daniel C. Masison, Herman K. Edskes
{"title":"[URE3] and [PSI] as prions ofSaccharomyces cerevisiae: genetic evidence and biochemical properties","authors":"Reed B. Wickner, Daniel C. Masison, Herman K. Edskes","doi":"10.1006/smvy.1996.0027","DOIUrl":"10.1006/smvy.1996.0027","url":null,"abstract":"<div><p>We have proposed that the yeast non-Mendelian elements [URE3] and [PSI] are prions, altered forms of Ure2p and Sup35p, respectively. Both are curable, but can arise again in the cured strains. The relation of the<em>ure2</em>and<em>sup35</em>mutations to [URE3] and [PSI] is that expected of prions, not that expected of nucleic acid replicons. Overproduction of Ure2p and Sup35p increases by 100-fold the frequency with which [URE3[ and [PSI] arise, respectively. The N-terminal 65 amino acid residues of Ure2p are necessary for the [URE3] change and Ure2p becomes partially protease-resistant in [URE3] strains. The chaperone, Hsp104, is necessary for the propagation of [PSI], but when overexpressed cures [PSI].</p></div>","PeriodicalId":92955,"journal":{"name":"Seminars in virology","volume":"7 3","pages":"Pages 215-223"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smvy.1996.0027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51137872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stanley B. Prusiner, Glenn Telling, Fred E. Cohen, Stephen J. DeArmond
{"title":"Prion diseases of humans and animals","authors":"Stanley B. Prusiner, Glenn Telling, Fred E. Cohen, Stephen J. DeArmond","doi":"10.1006/smvy.1996.0021","DOIUrl":"10.1006/smvy.1996.0021","url":null,"abstract":"Abstract Prions cause infectious and genetic neurodegenerative diseases. Transmissible prion particles are composed largely, if not entirely, of an abnormal isoform of the prion protein (PrPSc), which is encoded by a chromosomal gene. A post-translational process involving a profound conformational change converts the cellular prion protein (PrPC) into PrPSc. PrPChas a high α-helix content and is devoid of β-sheet; whereas, PrPSchas a lower α-helix content but is high in β-sheet. Transgenetic studies argue that a factor(s) designated protein X functions in the formation of PrPSc, perhaps as a molecular chaperone. Mutations in the PrP gene are genetically linked to development of neurodegeneration in humans. These mutations may cause disease by destabilizing one or more of the α-helices of PrPC. Investigations of prion diseases may give insights into the more common neurodegenerative diseases.","PeriodicalId":92955,"journal":{"name":"Seminars in virology","volume":"7 3","pages":"Pages 159-173"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smvy.1996.0021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51136399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spectroscopic conformational studies of prion protein isoforms and the mechanism of transformation","authors":"Jiri Safar","doi":"10.1006/smvy.1996.0026","DOIUrl":"10.1006/smvy.1996.0026","url":null,"abstract":"<div><p>The agent responsible for transmission of spongiform encephalopathies (prion diseases) has unique biological and physical properties, and its essential component is the prion protein (scrapie amyloid). The recent developments in structural chemistry and molecular biology of the prion protein provide strong evidence for the central role of an abnormal post-translational protein folding mechanism in the transmission and pathogenesis of disease. During the course of disease, the normal chromosomal PrP gene product containing a predominantly α-helical secondary structure is transformed into a protein with more secondary structure in β-sheets. As a result, the protein acquires different physical properties and the ability to form amyloid. Understanding this apparently conformational conversion mechanism may advance the investigation of other neurodegenerative disorders and brain amyloidoses. Here we review current knowledge of the structural chemistry of the prion protein and explore the mechanism of its replication.</p></div>","PeriodicalId":92955,"journal":{"name":"Seminars in virology","volume":"7 3","pages":"Pages 207-214"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smvy.1996.0026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51137805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bernardino Ghetti , Pedro Piccardo , Blas Frangione , Orso Bugiani , Giorgio Giaccone , Katherine Young , Frances Prelli , Martin R. Farlow , Stephen R. Dlouhy , Fabrizio Tagliavini
{"title":"Prion protein hereditary amyloidosis: parenchymal and vascular","authors":"Bernardino Ghetti , Pedro Piccardo , Blas Frangione , Orso Bugiani , Giorgio Giaccone , Katherine Young , Frances Prelli , Martin R. Farlow , Stephen R. Dlouhy , Fabrizio Tagliavini","doi":"10.1006/smvy.1996.0024","DOIUrl":"10.1006/smvy.1996.0024","url":null,"abstract":"<div><p>Prion protein (PrP) amyloidosis is a feature of Gerstmann-Sträussler-Scheinker disease (GSS) and prion protein cerebral amyloid angiopathy (PrP-CAA). GSS and PrP-CAA are associated with point mutations of the prion protein gene (PRNP); there is a broad spectrum of clinical presentations and the main signs are ataxia, spastic paraparesis, extrapyramidal signs and dementia. In GSS, parenchymal amyloid may be associated with spongiform changes or neurofibrillary lesions; in PrP-CAA, vascular amyloid is associated with neurofibrillary lesions. In the two diseases, a major component of the amyloid fibrils is a 7 kDa peptide, approximately spanning residues 81–150 of PrP.</p></div>","PeriodicalId":92955,"journal":{"name":"Seminars in virology","volume":"7 3","pages":"Pages 189-200"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smvy.1996.0024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51137794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transmissible mink encephalopathy","authors":"McKenzie D., Bartz J.C., Marsh R.F.","doi":"10.1006/smvy.1996.0025","DOIUrl":"10.1006/smvy.1996.0025","url":null,"abstract":"<div><p>Transmissible mink encephalopathy is a rare disease of ranch-raised mink that is caused by exposure to a scrapie-like agent in feed. Transmission of TME to hamsters resulted in the identification of two clinically different syndromes, HYPER and DROWSY. Differences in the physicochemical properties of PrP from these two strains suggests that PrP plays an important role in defining strains. This review will summarize what is currently known about TME and relate it to the broader field of transmissible spongiform encephalopathies.</p></div>","PeriodicalId":92955,"journal":{"name":"Seminars in virology","volume":"7 3","pages":"Pages 201-206"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smvy.1996.0025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87432093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher J. Miller, Michael B. McChesney, Xusheng Lü
{"title":"Mucosal immune responses to SIV infection","authors":"Christopher J. Miller, Michael B. McChesney, Xusheng Lü","doi":"10.1006/smvy.1996.0018","DOIUrl":"10.1006/smvy.1996.0018","url":null,"abstract":"<div><p>We have begun the process of characterizing the mucosal immune responses to SIV in the SIV/rhesus macaque system. We demonstrate that anti-SIV antibodies are found in the vaginal secretions, rectal secretions, saliva and serum of SIV-infected rhesus macaques and that IgG is the major anti-SIV antibody isotype in vaginal secretions and saliva. We have provided the first demonstration that anti-SIV cytotoxic T lymphocytes are present in the vaginal epithelium of SIV-infected rhesus macaques. The work described here clearly shows the existence of both cellular and humoral anti-SIV immune responses in the genital tract of SIV-infected female rhesus macaques.</p></div>","PeriodicalId":92955,"journal":{"name":"Seminars in virology","volume":"7 2","pages":"Pages 139-145"},"PeriodicalIF":0.0,"publicationDate":"1996-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smvy.1996.0018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51136243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Costimulatory signals and viral immunity","authors":"Arlene H. Sharpe","doi":"10.1006/smvy.1996.0013","DOIUrl":"10.1006/smvy.1996.0013","url":null,"abstract":"<div><p>Costimulation plays a pivotal role in T-cell activation, since engagement of the T-cell receptor in the absence of costimulatory signals can lead to T-cell anergy. The B7-CD28/CTLA4 costimulatory pathway can provide a potent costimulatory signal. This article focuses on the B7-CD28/CTLA4 pathway, reviewing aspects of costimulation relevant to the development of anti-viral immune responses and summarizing vaccination strategies employing costimulatory molecules. In addition, this article discusses the importance of regulated expression of costimulatory molecules and describes how viruses can modulate the expression of costimulatory molecules, which may contribute to immune dysfunction.</p></div>","PeriodicalId":92955,"journal":{"name":"Seminars in virology","volume":"7 2","pages":"Pages 103-111"},"PeriodicalIF":0.0,"publicationDate":"1996-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/smvy.1996.0013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51135903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}