Alteration of Prion Strain Emergence by Nonhost Factors

ABSTRACT Prions can persist in the environment for extended periods of time after adsorption to surfaces, including soils, feeding troughs, or fences. Prion strain- and soil-specific differences in prion adsorption, infectivity, and response to inactivation may be involved in strain maintenance or e...

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Autores principales:	Sara A. M. Holec, Qi Yuan, Jason C. Bartz
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	prion strain strain emergence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/12f1f1b3bb6243c2b99519772f5e8172
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spelling	oai:doaj.org-article:12f1f1b3bb6243c2b99519772f5e81722021-11-15T15:27:33ZAlteration of Prion Strain Emergence by Nonhost Factors10.1128/mSphere.00630-192379-5042https://doaj.org/article/12f1f1b3bb6243c2b99519772f5e81722019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00630-19https://doaj.org/toc/2379-5042ABSTRACT Prions can persist in the environment for extended periods of time after adsorption to surfaces, including soils, feeding troughs, or fences. Prion strain- and soil-specific differences in prion adsorption, infectivity, and response to inactivation may be involved in strain maintenance or emergence of new strains in a population. Extensive proteinase K (PK) digestion of Hyper (HY) and Drowsy (DY) PrPSc resulted in a greater reduction in the level of DY PrPSc than of HY PrPSc. Use of the PK-digested material in protein misfolding cyclic amplification strain interference (PMCAsi) resulted in earlier emergence of HY PrPSc than of undigested controls. This result established that strain-specific alteration of the starting ratios of conversion-competent HY and DY PrPSc can alter strain emergence. We next investigated whether environmentally relevant factors such as surface binding and weathering could alter strain emergence. Adsorption of HY and DY PrPSc to silty clay loam (SCL), both separately and combined, resulted in DY interfering with the emergence of HY in PMCAsi in a manner similar to that seen with unbound controls. Similarly, repeated cycles of wetting and drying of SCL-bound HY and DY PrPSc did not alter the emergence of HY PrPSc compared to untreated controls. Importantly, these data indicate that prion strain interference can occur when prions are bound to surfaces. Interestingly, we found that drying of adsorbed brain homogenate on SCL could restore its ability to interfere with the emergence of HY, suggesting a novel strain interference mechanism. Overall, these data provide evidence that the emergence of a strain from a mixture can be influenced by nonhost factors. IMPORTANCE The prion strain, surface type, and matrix containing PrPSc can influence PrPSc surface adsorption. The cumulative effect of these factors can result in strain- and soil-specific differences in prion bioavailability. Environmental weathering processes can result in decreases in PrPSc conversion efficiency and infectivity. Little is known about how incomplete inactivation of surface-bound PrPSc affects transmission and prion strain emergence. Here, we show that strain interference occurs with soil-bound prions and that altering the ratios of prion strains by strain-specific inactivation can affect strain emergence. Additionally, we identify a novel mechanism of inhibition of prion conversion by environmental treatment-induced changes at the soil-protein interface altering strain emergence. These novel findings suggest that environmental factors can influence strain emergence of surface-bound prions.Sara A. M. HolecQi YuanJason C. BartzAmerican Society for Microbiologyarticleprionstrainstrain emergenceMicrobiologyQR1-502ENmSphere, Vol 4, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	prion strain strain emergence Microbiology QR1-502
spellingShingle	prion strain strain emergence Microbiology QR1-502 Sara A. M. Holec Qi Yuan Jason C. Bartz Alteration of Prion Strain Emergence by Nonhost Factors
description	ABSTRACT Prions can persist in the environment for extended periods of time after adsorption to surfaces, including soils, feeding troughs, or fences. Prion strain- and soil-specific differences in prion adsorption, infectivity, and response to inactivation may be involved in strain maintenance or emergence of new strains in a population. Extensive proteinase K (PK) digestion of Hyper (HY) and Drowsy (DY) PrPSc resulted in a greater reduction in the level of DY PrPSc than of HY PrPSc. Use of the PK-digested material in protein misfolding cyclic amplification strain interference (PMCAsi) resulted in earlier emergence of HY PrPSc than of undigested controls. This result established that strain-specific alteration of the starting ratios of conversion-competent HY and DY PrPSc can alter strain emergence. We next investigated whether environmentally relevant factors such as surface binding and weathering could alter strain emergence. Adsorption of HY and DY PrPSc to silty clay loam (SCL), both separately and combined, resulted in DY interfering with the emergence of HY in PMCAsi in a manner similar to that seen with unbound controls. Similarly, repeated cycles of wetting and drying of SCL-bound HY and DY PrPSc did not alter the emergence of HY PrPSc compared to untreated controls. Importantly, these data indicate that prion strain interference can occur when prions are bound to surfaces. Interestingly, we found that drying of adsorbed brain homogenate on SCL could restore its ability to interfere with the emergence of HY, suggesting a novel strain interference mechanism. Overall, these data provide evidence that the emergence of a strain from a mixture can be influenced by nonhost factors. IMPORTANCE The prion strain, surface type, and matrix containing PrPSc can influence PrPSc surface adsorption. The cumulative effect of these factors can result in strain- and soil-specific differences in prion bioavailability. Environmental weathering processes can result in decreases in PrPSc conversion efficiency and infectivity. Little is known about how incomplete inactivation of surface-bound PrPSc affects transmission and prion strain emergence. Here, we show that strain interference occurs with soil-bound prions and that altering the ratios of prion strains by strain-specific inactivation can affect strain emergence. Additionally, we identify a novel mechanism of inhibition of prion conversion by environmental treatment-induced changes at the soil-protein interface altering strain emergence. These novel findings suggest that environmental factors can influence strain emergence of surface-bound prions.
format	article
author	Sara A. M. Holec Qi Yuan Jason C. Bartz
author_facet	Sara A. M. Holec Qi Yuan Jason C. Bartz
author_sort	Sara A. M. Holec
title	Alteration of Prion Strain Emergence by Nonhost Factors
title_short	Alteration of Prion Strain Emergence by Nonhost Factors
title_full	Alteration of Prion Strain Emergence by Nonhost Factors
title_fullStr	Alteration of Prion Strain Emergence by Nonhost Factors
title_full_unstemmed	Alteration of Prion Strain Emergence by Nonhost Factors
title_sort	alteration of prion strain emergence by nonhost factors
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/12f1f1b3bb6243c2b99519772f5e8172
work_keys_str_mv	AT saraamholec alterationofprionstrainemergencebynonhostfactors AT qiyuan alterationofprionstrainemergencebynonhostfactors AT jasoncbartz alterationofprionstrainemergencebynonhostfactors
_version_	1718427932330819584

Alteration of Prion Strain Emergence by Nonhost Factors

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