When two prion strains infect a single host, one strain can interfere with the ability of the other to cause disease but it is not known whether prion replication of the second strain is also diminished. To further investigate strain interference, we infected hamsters in the sciatic nerve with the long-incubation-period transmissible mink encephalopathy (TME) agent DY TME prior to superinfection of hamsters with the short-incubation-period HY TME agent. Increases in the interval between TME agent inoculations resulted in an extension of the incubation period of HY TME or a complete block of the ability of the HY TME agent to cause disease. The sciatic nerve route of inoculation gave the two TME strains access to the same population of neurons, allowing for the potential of prion interference in the lumbar spinal cord. The ability of the DY TME agent to extend the incubation period of HY TME corresponds with detection of DY TME PrP Sc , the abnormal isoform of the prion protein, in the lumbar spinal cord. The increased incubation period of HY TME or the inability of the HY TME agent to cause disease in the coinfected animals corresponds with a reduction in the abundance of HY TME PrP Sc 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 TME and DY TME did not occur. This suggests that DY TME agent replication interferes with HY TME agent replication when the two strains infect a common population of neurons.Prion diseases are a group of emerging, transmissible, neurodegenerative diseases of humans and animals that are inevitably fatal. Two cases of variant Creutzfeldt-Jakob disease (vCJD) were identified in humans who received blood transfusions from asymptomatic individuals who later developed vCJD. These cases suggest that vCJD can be transmitted from human to human via blood prior to the onset of clinical symptoms (27, 32). The recent identification of multiple PrP Sc types in vCJD brain tissue suggests that more than one prion strain may be present in field isolates of vCJD (33). Passage of vCJD agents between humans could result in further adaptation of vCJD, resulting in a selection of prion strains that have increased human pathogenicity.The mechanism of prion adaptation is beginning to be understood. Rodent transmission studies suggest that after intraspecies transmission, prion strains are selected from a mixture or from new strains that arose from a single strain present in the original inoculum (16,19,22). Experimental inoculation of individual animals with two prion strains has allowed the biological parameters of strain selection to be characterized. Experimental coinfection of mice with two prion strains was first described with the long-incubation-period scrapie agent strain 22C and the short-incubation-period scrapie agent strain 22A (14). In these experiments, the longincubation-period strain (i.e., the blocking strain) 22C was intracerebrally inoculated prior to intracerebral inoculation (i.e...

Prion diseases are emerging infectious disorders that affect several mammalian species including humans. The transmissible agent is comprised of PrP Sc , a misfolded isoform of the normal host-encoded prion protein PrP C . Immunodetection of PrP Sc is often utilized for prion disease diagnosis and tracking spread of the infectious agent through the host. We have developed a rapid, high-throughput 96-well immunoassay, which is specific for the detection of PrP Sc . This assay has PrP Sc detection limits similar to western blot and is advantageous because of its comparatively shorter running time, smaller start-up and operation costs and large sample capacity.