Prion strain mutation determined by prion protein conformational compatibility and primary structure.
Prions are infectious proteins composed of the abnormal disease-causing isoform PrPSc, which induces conformational conversion of the host-encoded normal cellular prion protein PrPC to additional PrPSc. The mechanism underlying prion strain mutation in the absence of nucleic acids remains unresolved. Additionally, the frequency of strains causing chronic wasting disease (CWD), a burgeoning prion epidemic of cervids, is unknown. Using susceptible transgenic mice, we identified two prevalent CWD strains with divergent biological properties but composed of PrPSc with indistinguishable biochemical characteristics. Although CWD transmissions indicated stable, independent strain propagation by elk PrPC, strain coexistence in the brains of deer and transgenic mice demonstrated unstable strain propagation by deer PrPC. The primary structures of deer and elk prion proteins differ at residue 226, which, in concert with PrPSc conformational compatibility, determines prion strain mutation in these cervids.
Angers
Rachel C
RC
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky Medical Center, Lexington, KY 40536, USA.
Kang
Hae-Eun
HE
Napier
Dana
D
Browning
Shawn
S
Seward
Tanya
T
Mathiason
Candace
C
Balachandran
Aru
A
McKenzie
Debbie
D
Castilla
Joaquín
J
Soto
Claudio
C
Jewell
Jean
J
Graham
Catherine
C
Hoover
Edward A
EA
Telling
Glenn C
GC
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D003670:Deer; D004198:Disease Susceptibility; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D018621:PrPC Proteins / Q000737:chemistry* / Q000235:genetics; D018620:PrPSc Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000472:pathogenicity; D011487:Protein Conformation; D017510:Protein Folding; D012641:Selection, Genetic; D012692:Serial Passage; D013045:Species Specificity; D034081:Wasting Disease, Chronic / Q000473:pathology / Q000635:transmission
D018621:PrPC Proteins; D018620:PrPSc Proteins
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