Replication Efficiency of Soil-Bound Prions Varies with Soil Type

Saunders, Samuel E.; Shikiya, Ronald A.; Langenfeld, Katie; Bartelt–Hunt, Shannon L.; Bartz, Jason C.

doi:10.1128/jvi.00282-11

Cited by 57 publications

(91 citation statements)

References 42 publications

(67 reference statements)

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“…There are a number of environmental sources of infectious prions, including decaying carcasses (34), placenta (35,36), antler velvet (37), blood (38)(39)(40)(41)(42), urine (43)(44)(45)(46), and feces (47)(48)(49)(50), that could be inhaled into the NC and horizontally transmit disease (7,8) in both captive and free-ranging animal populations. It is worth noting that soil-bound prions remain infectious (19,(51)(52)(53) and that the physical size of the intercellular spaces reported here would accommodate the particle size of silt and clay (between 2 and 50 m), allowing infection from inhaled contaminated soil. Also, the indiscriminate bulk transport of prions following inhalation is consistent with the growing body of work that demonstrates that prions are transported in strain-independent ways (54,55).…”

Section: Discussionmentioning

confidence: 99%

Specificity, Size, and Frequency of Spaces That Characterize the Mechanism of Bulk Transepithelial Transport of Prions in the Nasal Cavities of Hamsters and Mice

Kincaid

Ayers

Bartz

2016

J Virol

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Inhalation of infected brain homogenate results in transepithelial transport. Bulk transepithelial transport in the nasal cavity has not been studied to date. In the present study, we characterized the frequency, size, and specificity of the intercellular spaces that mediate the bulk transport of inhaled prions between cells of mice or hamsters following extranasal inoculation with mock-infected brain homogenate, different strains of prion-infected brain homogenate, or brain homogenate mixed with India ink. Infected or mock-infected inoculum was identified within lymphatic vessels of the lamina propria and in spaces of >5 m between a small number of cells of the nasal mucosa in >90% of animals from 5 to 60 min after inhalation. The width of the spaces between cells, the amount of the inoculum within the lumen of lymphatic vessels, and the timing of the transport indicate that this type of transport was taking place through preexisting spaces in the nasal cavity that were orders of magnitude wider than what is normally reported for paracellular transport. The indiscriminate rapid bulk transport of brain homogenate in the nasal cavity results in immediate entry into nasal cavity lymphatics following inhalation. This novel mechanism may underlie the recent report of the early detection of prions in blood following inhalation and has implications for horizontal prion transmission. IMPORTANCEThe results of these studies demonstrate that the nasal mucosa of mice and hamsters is not an absolute anatomical barrier to inhaled prion-infected or uninfected brain homogenate. Relatively large amounts of infected and uninfected brain homogenate rapidly cross the nasal mucosa and enter the lumen of lymphatic vessels following inhalation. These bulk transepithelial transport events were relatively rare but present in >90% of animals 5 to 60 min following inhalation. This novel mechanism of bulk transepithelial transport was seen in experimental and control hamsters and mice, indicating that it was not species specific or in response to prion exposure. The indiscriminate bulk intercellular transport of inhaled pathogens across the nasal mucosa followed by entry into the lymphatic system may be a mechanism that underlies the entry and spread of other toxins and pathogens in olfactory system-driven animals.T ransmissible spongiform encephalopathies (TSEs) are a group of fatal neurological disorders affecting a variety of animal species, including humans. TSEs have relatively long incubation periods, and although they are rare in humans, they are relatively common in some animal populations. The TSEs affecting animals include scrapie in sheep and goats and chronic wasting disease (CWD) in deer, elk, and moose. The infectious agent is thought to consist largely if not entirely of PrP Sc , a misfolded conformation of the naturally occurring prion protein (PrP), designated PrP C (1-6). Specific details of the transmission of these diseases are not known, but there is evidence for the horizontal transmission of PrP Sc that has...

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Section: Discussionmentioning

confidence: 99%

Specificity, Size, and Frequency of Spaces That Characterize the Mechanism of Bulk Transepithelial Transport of Prions in the Nasal Cavities of Hamsters and Mice

Kincaid

Ayers

Bartz

2016

J Virol

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“…The relationship between the titer of the inoculum and the incubation period is highly reproducible (5,7,18,32,40). By calculation of the titers of the brain-derived and PMCA-generated HY TME agents (Table 1), the relationship between inoculum titer and incubation period was established (Table 2).…”

Section: Prpmentioning

confidence: 99%

In Vitro Generation of High-Titer Prions

Shikiya¹,

Bartz

2011

J Virol

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Prions are composed mainly, if not entirely, of PrPSc , an infectious misfolded isoform of PrP C , the normal isoform of the prion protein. Here we show that protein misfolding cyclic amplification (PMCA)-generated hypertransmissible mink encephalopathy (HY TME) PrP Sc is highly infectious and has a titer that is similar, if not identical, to that associated with brain tissue from animals infected with the HY TME agent that are in the terminal stage of disease. These data demonstrate that PMCA efficiently replicates the prion agent and provide further support for the hypothesis that in vitro-generated prions are bona fide and are not due to contamination.

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“…Thus, the facile transmission of CWD, coupled with its growing geographical distribution (19) and propensity to persist in the environment (20)(21)(22), provide ample opportunity for the bioavailability of CWD prions to many species coexisting with CWD in nature, including felids.…”

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confidence: 99%