TY - JOUR
T1 - Incongruity between prion conversion and incubation period following coinfection
AU - Langenfeld, Katie A.
AU - Shikiya, Ronald A.
AU - Kincaid, Anthony E.
AU - Bartz, Jason C.
N1 - Funding Information:
This work, including the efforts of Katie A. Langenfeld, was funded by HHS | National Institutes of Health (NIH). This work, including the efforts of Jason C. Bartz, was funded by HHS | NIH | National Center for Research Resources (NCRR) (P20 RR0115635-6 and C06 RR17417-01). This work, including the efforts of Jason C. Bartz, was funded by HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) (R01 NS052609).
Publisher Copyright:
© 2016, American Society for Microbiology.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - When multiple prion strains are inoculated into the same host, they can interfere with each other. Strains with long incubation periods can suppress conversion of strains with short incubation periods; however, nothing is known about the conversion of the long-incubation-period strain during strain interference. To investigate this, we inoculated hamsters in the sciatic nerve with long-incubation-period strain 139H prior to superinfection with the short-incubation-period hyper (HY) strain of transmissible mink encephalopathy (TME). First, we found that 139H is transported along the same neuroanatomical tracks as HY TME, adding to the growing body of evidence indicating that PrPSc favors retrograde transneuronal transport. In contrast to a previous report, we found that 139H interferes with HY TME infection, which is likely due to both strains targeting the same population of neurons following sciatic nerve inoculation. Under conditions where 139H blocked HY TME from causing disease, the strainspecific properties of PrPSc corresponded with the strain that caused disease, consistent with our previous findings. In the groups of animals where incubation periods were not altered, we found that the animals contained a mixture of 139H and HY TME PrPSc. This finding expands the definition of strain interference to include conditions where PrPSc formation is altered yet disease outcome is unaltered. Overall, these results contradict the premise that prion strains are static entities and instead suggest that strain mixtures are dynamic regardless of incubation period or clinical outcome of disease.
AB - When multiple prion strains are inoculated into the same host, they can interfere with each other. Strains with long incubation periods can suppress conversion of strains with short incubation periods; however, nothing is known about the conversion of the long-incubation-period strain during strain interference. To investigate this, we inoculated hamsters in the sciatic nerve with long-incubation-period strain 139H prior to superinfection with the short-incubation-period hyper (HY) strain of transmissible mink encephalopathy (TME). First, we found that 139H is transported along the same neuroanatomical tracks as HY TME, adding to the growing body of evidence indicating that PrPSc favors retrograde transneuronal transport. In contrast to a previous report, we found that 139H interferes with HY TME infection, which is likely due to both strains targeting the same population of neurons following sciatic nerve inoculation. Under conditions where 139H blocked HY TME from causing disease, the strainspecific properties of PrPSc corresponded with the strain that caused disease, consistent with our previous findings. In the groups of animals where incubation periods were not altered, we found that the animals contained a mixture of 139H and HY TME PrPSc. This finding expands the definition of strain interference to include conditions where PrPSc formation is altered yet disease outcome is unaltered. Overall, these results contradict the premise that prion strains are static entities and instead suggest that strain mixtures are dynamic regardless of incubation period or clinical outcome of disease.
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U2 - 10.1128/JVI.00409-16
DO - 10.1128/JVI.00409-16
M3 - Article
C2 - 27053546
AN - SCOPUS:84971462346
VL - 90
SP - 5715
EP - 5723
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 12
ER -