Abstract
Prion strains are characterized by strain-specific differences in neuropathology but can also differ in incubation period, clinical disease, host-range and tissue tropism. The hyper (HY) and drowsy (DY) strains of hamster-adapted transmissible mink encephalopathy (TME) differ in tissue tropism and susceptibility to infection by extraneural routes of infection. Notably, DY TME is not detected in the secondary lymphoreticular system (LRS) tissues of infected hosts regardless of the route of inoculation. We found that similar to the lymphotropic strain HY TME, DY TME crosses mucosal epithelia, enters draining lymphatic vessels in underlying laminae propriae, and is transported to LRS tissues. Since DY TME causes disease once it enters the peripheral nervous system, the restriction in DY TME pathogenesis is due to its inability to establish infection in LRS tissues, not a failure of transport. To determine if LRS tissues can support DY TME formation, we performed protein misfolding cyclic amplification using DY PrPScas the seed and spleen homogenate as the source of PrPC. We found that the spleen environment can support DY PrPScformation, although at lower rates compared to lymphotropic strains, suggesting that the failure of DY TME to establish infection in the spleen is not due to the absence of a strain-specific conversion cofactor. Finally, we provide evidence that DY PrPScis more susceptible to degradation when compared to PrPScfrom other lymphotrophic strains. We hypothesize that the relative rates of PrPScformation and clearance can influence prion tropism.
| Original language | English (US) |
|---|---|
| Article number | e1006298 |
| Journal | PLoS Pathogens |
| Volume | 13 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2017 |
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All Science Journal Classification (ASJC) codes
- Parasitology
- Microbiology
- Immunology
- Molecular Biology
- Genetics
- Virology
Cite this
PrPScformation and clearance as determinants of prion tropism. / Shikiya, Ronald A.; Langenfeld, Katie A.; Eckland, Thomas E.; Trinh, Jonathan; Holec, Sara A M; Mathiason, Candace K.; Kincaid, Anthony; Bartz, Jason C.
In: PLoS Pathogens, Vol. 13, No. 3, e1006298, 01.03.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PrPScformation and clearance as determinants of prion tropism
AU - Shikiya, Ronald A.
AU - Langenfeld, Katie A.
AU - Eckland, Thomas E.
AU - Trinh, Jonathan
AU - Holec, Sara A M
AU - Mathiason, Candace K.
AU - Kincaid, Anthony
AU - Bartz, Jason C.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Prion strains are characterized by strain-specific differences in neuropathology but can also differ in incubation period, clinical disease, host-range and tissue tropism. The hyper (HY) and drowsy (DY) strains of hamster-adapted transmissible mink encephalopathy (TME) differ in tissue tropism and susceptibility to infection by extraneural routes of infection. Notably, DY TME is not detected in the secondary lymphoreticular system (LRS) tissues of infected hosts regardless of the route of inoculation. We found that similar to the lymphotropic strain HY TME, DY TME crosses mucosal epithelia, enters draining lymphatic vessels in underlying laminae propriae, and is transported to LRS tissues. Since DY TME causes disease once it enters the peripheral nervous system, the restriction in DY TME pathogenesis is due to its inability to establish infection in LRS tissues, not a failure of transport. To determine if LRS tissues can support DY TME formation, we performed protein misfolding cyclic amplification using DY PrPScas the seed and spleen homogenate as the source of PrPC. We found that the spleen environment can support DY PrPScformation, although at lower rates compared to lymphotropic strains, suggesting that the failure of DY TME to establish infection in the spleen is not due to the absence of a strain-specific conversion cofactor. Finally, we provide evidence that DY PrPScis more susceptible to degradation when compared to PrPScfrom other lymphotrophic strains. We hypothesize that the relative rates of PrPScformation and clearance can influence prion tropism.
AB - Prion strains are characterized by strain-specific differences in neuropathology but can also differ in incubation period, clinical disease, host-range and tissue tropism. The hyper (HY) and drowsy (DY) strains of hamster-adapted transmissible mink encephalopathy (TME) differ in tissue tropism and susceptibility to infection by extraneural routes of infection. Notably, DY TME is not detected in the secondary lymphoreticular system (LRS) tissues of infected hosts regardless of the route of inoculation. We found that similar to the lymphotropic strain HY TME, DY TME crosses mucosal epithelia, enters draining lymphatic vessels in underlying laminae propriae, and is transported to LRS tissues. Since DY TME causes disease once it enters the peripheral nervous system, the restriction in DY TME pathogenesis is due to its inability to establish infection in LRS tissues, not a failure of transport. To determine if LRS tissues can support DY TME formation, we performed protein misfolding cyclic amplification using DY PrPScas the seed and spleen homogenate as the source of PrPC. We found that the spleen environment can support DY PrPScformation, although at lower rates compared to lymphotropic strains, suggesting that the failure of DY TME to establish infection in the spleen is not due to the absence of a strain-specific conversion cofactor. Finally, we provide evidence that DY PrPScis more susceptible to degradation when compared to PrPScfrom other lymphotrophic strains. We hypothesize that the relative rates of PrPScformation and clearance can influence prion tropism.
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U2 - 10.1371/journal.ppat.1006298
DO - 10.1371/journal.ppat.1006298
M3 - Article
VL - 13
JO - PLoS Pathogens
JF - PLoS Pathogens
SN - 1553-7366
IS - 3
M1 - e1006298
ER -