Effects of Elk-PrPC expression levels on CWD strain properties

Duque Velásquez, Camilo ; Otero, Alicia ; Kim, Chiye ; Triscott, Elizabeth ; Narayan, Jeffrey ; Van der Merwe, Jacques ; Aiken, Judd ; McKenzie, Debbie

Resumen: Chronic Wasting Disease (CWD) is a contagious prion disease affecting various species of free-ranging and/or captive cervids on three continents. Species-specific prion protein (PrPC) polymorphisms influence prion conversion into PrPCWD. PrPC amino acid variation can also regulate disease susceptibility to particular prion strains and has been implicated in the diversification of prion strain conformers [1, 2, 3]. Elk and deer PrPC differ at residue E226Q and this amino acid difference has been implicated in the selection of CWD1 and CWD2 prion strains [4]. As PrPC expression has been suggested to affect prion strain evolution [5], we hypothesized that elk PrPC levels affect CWD strain generation. To test this hypothesis, transgenic (tg) FVB mice over-expressing elk PrPC [6] were crossed with prnp knock-out FVB mice to generate tg-elk with different PrPC expression levels. Both tg-elk+/+ and tg-elk± were exposed to white-tailed deer CWD strains (Wisc-1 and H95+) [2, 3]. The H95+ strain was a mixture generated on passage of Wisc-1 in deer heterozygous for H95G96 and Q95S96 [2]. Tg-elk+/+ mice succumbed to Wisc-1 with a mean incubation period of 116 ± 7 days post infection (dpi) compared to 164 ± 11 dpi for the H95+ strain mixture. Consistent with the reduced PrPC expression, the same deer prion strains resulted in longer incubation periods (157 ± 21 dpi and >180 dpi, respectively) when passaged in tg-elk± mice. After first passage, transmission of Wisc-1 and H95+ in tg-elk+/+ mice resulted in a single neuropathological profile that differed from the profile produced by passage of elk prions (described as the CWD2 strain [1]). Our results show that, upon first passage, the E226Q polymorphism did not affect the strain properties of deer prions and indicates a single strain (Wisc-1) was selected by the tg-elk+/+ mice. The comparative analysis of neuropathological profiles between high and low expression tg-elk on first and second passage will be presented.

Idioma: Inglés

Año: 2019

Publicado en: Prion 13, Suppl 1 (2019), 76-77
ISSN: 1933-6896

Factor impacto JCR: 1.952 (2019)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 233 / 297 = 0.785 (2019) - Q4 - T3

Factor impacto SCIMAGO: 0.593 - Biochemistry (Q3) - Infectious Diseases (Q3) - Cell Biology (Q3) - Cellular and Molecular Neuroscience (Q4)

Tipo y forma: Artículo (Versión definitiva)