NR AXIX
AU Bartz,J.; Bessen,R.; Kincaid,A.
TI Prion Strain Interference in the Central Nervous System
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Oral Abstracts FC2.4
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB
Background: Prion strains can interfere with each other. Infection of a host with a slowly replicating prion strain (i.e. blocking strain) prior to superinfection with a quickly replicating strain can extend the incubation period, or completely block the superinfecting strain from causing disease. The ability of the blocking strain to interfere with or completely block the superinfecting strain is dependant on the interval between inoculation of the prion strains.
Objectives: 1) Determine if replication of the blocking strain is required for interference to occur. 2) Investigate the affect of the blocking strain on the replication of the superinfecting prion strain. 3) Identify the location of strain interference in the central
nervous system.
Methods: Hamsters were infected in the sciatic nerve with the long incubation period drowsy (DY) transmissible mink encephalopathy (TME) agent 60, 90 or 120 days prior to sciatic nerve superinfection of hamsters with the short incubation period hyper (HY) TME agent. Western blot and immunohistochemistry were used to determine the abundance and distribution of HY and DY PrPsc.
Results: Increasing the interval between TME agent inoculations resulted in an extension of the HY TME incubation period or a complete block of the HY TME agent to cause disease. The ability of the DY TME agent to extend the incubation period of HY TME corresponded with detection of DY PrPsc in the lumbar spinal cord. The increase in the incubation period of HY TME or inability of HY TME to cause disease in the co-infected animals corresponded with a reduction in the abundance of HY PrPsc in the lumbar spinal cord. When the two strains were not directed to the same populations of neurons within the lumbar spinal cord, interference between HY and DY TME did not occur.
Discussion: This data suggests that DY TME agent replication not only interferes with the ability of the HY TME agent to cause disease, but also interferes with HY TME agent replication. The ability of the DY TME agent to interfere with replication of the HY TME agent is dependent on infection of a common population of neurons. Therefore, a critical parameter for prion strain interference is not if two prion strains are inoculated at the same time or separately, but when and where prion replication occurs.
AD J. Bartz, Creighton University, Medical Microbiology and Immunology, USA; R. Bessen, Montana State University, Veterinary Molecular Biology, USA; A. Kincaid, Creighton University, Physical Therapy, USA
SP englisch
PO Schottland