Transmission of New Bovine Prion to Mice

We previously reported that cattle were affected by a prion disorder that differed from bovine spongiform encephalopathy (BSE) by showing distinct molecular features of disease-associated protease-resistant prion protein (PrPres). We show that intracerebral injection of such isolates into C57BL/6 mice produces a disease with preservation of PrPres molecular features distinct from BSE

Molecular Typing of Protease-Resistant Prion Protein in Transmissible Spongiform Encephalopathies of Small Ruminants, France, 2002–2009

The agent that causes bovine spongiform encephalopathy (BSE) may be infecting small ruminants, which could have serious implications for human health. To distinguish BSE from scrapie and to examine the molecular characteristics of the protease-resistant prion protein (PrPres), we used a specifically designed Western blot method to test isolates from 648 sheep and 53 goats. During 2002–2009, classical non-Nor98 transmissible spongiform encephalopathy had been confirmed among ≈1.7 million small ruminants in France. Five sheep and 2 goats that showed a PrPres pattern consistent with BSE, or with the CH1641 experimental scrapie source, were identified. Later, bioassays confirmed infection by the BSE agent in 1 of the 2 goats. Western blot testing of the 6 other isolates showed an additional C-terminally cleaved PrPres product, with an unglycosylated band at ≈14 kDa, similar to that found in the CH1641 experimental scrapie isolate and different from the BSE isolate

Phenotypic diversity revealed in cattle prion diseases

Up until now, Bovine Spongiform Encephalopathy (BSE) was thought to be caused by just one pathogen, which explained the highly uniform features of the disease in cattle. Unexpectedly, among cattle diagnosed with BSE in France, we found six cases where the disease marker, i.e. the prion protein, had molecular features clearly distinct from those typically found in BSE. Furthermore, two other cases were recently identified in Italy, with features different both from typical BSE and from these six atypical cases in France. Histopathological features in these two Italian cases also strongly suggested that the disease affecting these animals might not have been BSE. Hypotheses on the origin of such atypical cases are being discussed.On considérait jusqu'alors que l'encéphalopathie spongiforme bovine (ESB) était liée à l'infection par un agent infectieux unique, expliquant les caractéristiques très uniformes de la maladie chez les bovins. De façon inattendue, nous avons rencontré en France six cas, parmi des bovins diagnostiqués comme atteints d'ESB, qui présentent des caractéristiques moléculaires de la protéine prion pathologique, marqueur de l'infection, tout à fait différentes de celles habituellement rencontrées dans l'ESB. Deux cas présentant des caractéristiques différentes, aussi bien de l'ESB typique que des 6 cas précédents, ont par ailleurs été identifiés récemment en Italie. Les éléments de caractérisation histopathologique de ces deux derniers cas suggèrent par ailleurs très fortement qu'il s'agit d'une maladie différente de l'ESB. Les hypothèses concernant l'origine de ces cas atypiques sont discutées

Transmission of Atypical Bovine Prions to Mice Transgenic for Human Prion Protein

To assess risk for cattle-to-human transmission of prions that cause uncommon forms of bovine spongiform encephalopathy (BSE), we inoculated mice expressing human PrP Met129 with field isolates. Unlike classical BSE agent, L-type prions appeared to propagate in these mice with no obvious transmission barrier. H-type prions failed to infect the mice

Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model

L-type BSE is a more likely candidate for the origin of TME than typical BSE

Atypical Bovine Spongiform Encephalopathies, France, 2001–2007

In France, through exhaustive active surveillance, ≈17.1 million adult cattle were tested for bovine spongiform encephalopathy from July 2001 through July 2007; ≈3.6 million were >8 years of age. Our retrospective Western blot study of all 645 confirmed cases found that 7 were H-type and 6 were L-type

Emergence of Classical BSE Strain Properties during Serial Passages of H-BSE in Wild-Type Mice

BACKGROUND: Two distinct forms of atypical spongiform encephalopathies (H-BSE and L-BSE) have recently been identified in cattle. Transmission studies in several wild-type or transgenic mouse models showed that these forms were associated with two distinct major strains of infectious agents, which also differed from the unique strain that had been isolated from cases of classical BSE during the food-borne epizootic disease. METHODOLOGY/PRINCIPAL FINDINGS: H-BSE was monitored during three serial passages in C57BL/6 mice. On second passage, most of the inoculated mice showed molecular features of the abnormal prion protein (PrP(d)) and brain lesions similar to those observed at first passage, but clearly distinct from those of classical BSE in this mouse model. These features were similarly maintained during a third passage. However, on second passage, some of the mice exhibited distinctly different molecular and lesion characteristics, reminiscent of classical BSE in C57Bl/6 mice. These similarities were confirmed on third passage from such mice, for which the same survival time was also observed as with classical BSE adapted to C57Bl/6 mice. Lymphotropism was rarely detected in mice with H-BSE features. In contrast, PrP(d) was detectable, on third passage, in the spleens of most mice exhibiting classical BSE features, the pattern being indistinguishable from that found in C57Bl/6 mice infected with classical BSE. CONCLUSION/SIGNIFICANCE: Our data demonstrate the emergence of a prion strain with features similar to classical BSE during serial passages of H-BSE in wild-type mice. Such findings might help to explain the origin of the classical BSE epizootic disease, which could have originated from a putatively sporadic form of BSE

Outbreak of Dengue and Chikungunya Fevers, Toamasina, Madagascar, 2006

An outbreak of dengue-like syndrome occurred in Toamasina from January through March 2006. Dengue type l or chikungunya viruses were detected in 38 of 55 patients sampled. Aedes albopictus was the only potential vector collected. Of 4,242 randomly selected representative residents interviewed retrospectively, 67.5% reported a dengue-like syndrome during this period

Clinical and Pathologic Features of H-Type Bovine Spongiform Encephalopathy Associated with E211K Prion Protein Polymorphism

The majority of bovine spongiform encephalopathy (BSE) cases have been ascribed to the classical form of the disease. H-type and L-type BSE cases have atypical molecular profiles compared to classical BSE and are thought to arise spontaneously. However, one case of H-type BSE was associated with a heritable E211K mutation in the prion protein gene. The purpose of this study was to describe transmission of this unique isolate of H-type BSE when inoculated into a calf of the same genotype by the intracranial route. Electroretinograms were used to demonstrate preclinical deficits in retinal function, and optical coherence tomography was used to demonstrate an antemortem decrease in retinal thickness. The calf rapidly progressed to clinical disease (9.4 months) and was necropsied. Widespread distribution of abnormal prion protein was demonstrated within neural tissues by western blot and immunohistochemistry. While this isolate is categorized as BSE-H due to a higher molecular mass of the unglycosylated PrPSc isoform, a strong labeling of all 3 PrPSc bands with monoclonal antibodies 6H4 and P4, and a second unglycosylated band at approximately 14 kDa when developed with antibodies that bind in the C-terminal region, it is unique from other described cases of BSE-H because of an additional band 23 kDa demonstrated on western blots of the cerebellum. This work demonstrates that this isolate is transmissible, has a BSE-H phenotype when transmitted to cattle with the K211 polymorphism, and has molecular features that distinguish it from other cases of BSE-H described in the literature