Modelling the effect of genotype (PRNP) linked to susceptibility, infection duration and prion shedding on chronic wasting disease dynamics of cervids
Author links open overlay panel Atle Mysterud a b † , Magnus Nygård Osnes c † , Katharine Rose Dean c , Stefan Widgren d , Michael A. Tranulis e , Hildegunn Viljugrein c a
Highlights
• The prion protein gene (PRNP) can change chronic wasting disease (CWD) dynamics.
• A stochastic SEID-model was developed to explore the impacts of different PRNP-alleles.
• Reduced susceptibility and level of shedding slowed epidemics.
• Longer duration of infection and prion shedding led to more persistent epidemics.
Abstract
Host genetics affect their susceptibility to pathogens and their ability to transmit infections (contagiousness). Chronic wasting disease (CWD) is a lethal prion disease of cervids with a wide distribution in North America, and with the first detection in Europe among reindeer in Norway in 2016. The PRNP gene, encoding the prion protein, has a strong impact on host susceptibility, and the duration and level of prion shedding. We developed a Susceptible-Exposed-Infectious-Dead (SEID) model to enhance our understanding of how PRNP genotype variation influences CWD dynamics. In a baseline model with only highly susceptible PRNP alleles, CWD prevalence reached a high level before the population collapsed. We sequentially introduced PRNP heterogeneity in susceptibility (Scenario 1), the duration of prion shedding (Scenario 2), and amount of prion shedding (Scenario 3). Heterogeneity in susceptibility alone (Scenario 1) led to a slow increase in CWD prevalence towards its peak, followed by a gradual decline and eventual epidemic die-out. Increasing the infection duration with constant shedding for the less susceptible PRNP genotypes (Scenario 2) led to a high and persistent CWD-prevalence level. When combining low-susceptibility PRNP alleles and increased duration of shedding but at lower levels (Scenario 3), the prevalence of CWD peaked slowly compared to the other scenarios. Hence, variation in PRNP allele composition can yield qualitatively different CWD epidemics among populations. Our ability to predict the long-term effects of CWD remains limited, primarily due to uncertainty about shedding patterns, environmental contamination, and other factors associated with PRNP-alleles that may limit selection.
Snip…
4.7. Management implications
PRNP guided selection of breeding rams has played a key role in the successful reduction of classical scrapie in sheep in Europe (Tranulis, 2002; Dawson et al., 2008). The limited effectiveness and unpopularity of CWD management actions (Uehlinger et al., 2016), such as hunter-harvest or culling, makes PRNP-guided breeding programs appealing. Breeding programs have been conducted for CWD in captive populations of deer in North America (Haley et al., 2021). In 2024, Oklahoma, USA, state legislature passed a bill called the “Chronic Wasting Disease Genetic Improvement Act” to breed white-tailed deer for more resistant genetics with the intent to release farm-raised deer that possess more resistant genetics into the wild (Bostian, 2024). Similarly, influential veterinarians in Norway have suggested to breed robust reindeer for release into the depopulated and fallowed area of Nordfjella (Mysterud et al., 2024). However, our paper highlights several important and persisting gaps in knowledge that limited our ability to predict the role of PRNP in CWD dynamics for reindeer and other cervids. Hence, caution should be taken when applying these findings to real-world situations.
“However, our paper highlights several important and persisting gaps in knowledge that limited our ability to predict the role of PRNP in CWD dynamics for reindeer and other cervids. Hence, caution should be taken when applying these findings to real-world situations.”
That’s an understatement imo…terry
Volume 30, Number 10—October 2024
Research
Temporal Characterization of Prion Shedding in Secreta of White-Tailed Deer in Longitudinal Study of Chronic Wasting Disease, United State
Our findings suggest that deer expressing alternative PRNP polymorphisms might live longer and, although they shed fewer prions throughout CWD course, might over their extended lifespan increase CWD prions in the environment…
Prion protein gene sequence and chronic wasting disease susceptibility in white-tailed deer (Odocoileus virginianus)
Adam L Brandt, Amy C Kelly, Michelle L Green, Paul Shelton, Jan Novakofski & Nohra E Mateus-Pinilla
Pages 449-462 | Received 21 Sep 2015, Accepted 23 Oct 2015, Published online: 21 Dec 2015 https://doi.org/10.1080/19336896.2015.1115179
The presence of aa96S has been associated with slowed disease progression, longer life span among captive deer,Citation26,27 and does not appear to affect the rate at which prions are shed from infected individuals.Citation38 Additionally, CWD infected mule deer have been found to excrete pathogenic prions while asymptomatic.Citation39 This contributes to concerns that wild deer with aa96S may be shedding infectious prions into the environment for longer periods of time than deer lacking the mutation, but are not symptomatic or detectable by immunohistochemical procedures.
https://www.tandfonline.com/doi/full/10.1080/19336896.2015.1115179#d1e354
https://pmc.ncbi.nlm.nih.gov/articles/PMC4964855/pdf/kprn-09-06-1115179.pdf
''There are no known familial or genetic TSEs of animals, although polymorphisms in the PRNP gene of some species (sheep for example) may influence the length of the incubation period and occurrence of disease.''
c) The commonest form of CJD occurs as a sporadic disease, the cause of which is unknown, although genetic factors (particularly the codon 129 polymorphism in the prion protein gene (PRNP)) influence disease susceptibility. The familial forms of human TSEs (see Box 1) appear to have a solely genetic origin and are closely associated with mutations or insertions in the PRNP gene. Most, but not all, of the familial forms of human TSEs have been transmitted experimentally to animals. There are no known familial or genetic TSEs of animals, although polymorphisms in the PRNP gene of some species (sheep for example) may influence the length of the incubation period and occurrence of disease.
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/209755/Part_1_-_Introduction.pdf
P-145 Estimating chronic wasting disease resistance in cervids using real time quaking- induced conversion
Nicholas J Haley1, Rachel Rielinqer2, Kristen A Davenport3, W. David Walter4, Katherine I O'Rourke5, Gordon Mitchell6, Juergen A Richt2 1
Our studies demonstrate that in vitro amplification metrics predict in vivo susceptibility, and that alleles with multiple codons, each influencing resistance independently, do not necessarily contribute additively to resistance. Importantly, we found that the white-tailed deer 226K substrate exhibited the slowest amplification rate among those evaluated, suggesting that further investigation of this allele and its resistance in vivo are warranted to determine if absolute resistance to CWD is possible. ***at present, no cervid PrP allele conferring absolute resistance to prion infection has been identified.
PRION 2016 CONFERENCE TOKYO
http://prion2016.org/dl/newsletter_03.pdf
http://chronic-wasting-disease.blogspot.com/2017/04/
***> at present, no PrPC allele conferring absolute resistance in cervids has been identified.
J Gen Virol. 2017 Nov; 98(11): 2882–2892.
Published online 2017 Oct 23. doi: 10.1099/jgv.0.000952
Estimating chronic wasting disease susceptibility in cervids using real-time quaking-induced conversion
Chronic wasting disease (CWD) resistance in cervids is often characterized as decreased prevalence and/or protracted disease progression in individuals with specific alleles; at present, no PrPC allele conferring absolute resistance in cervids has been identified.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845664/pdf/jgv-98-2882.pdf
https://pmc.ncbi.nlm.nih.gov/articles/PMC4964855/pdf/kprn-09-06-1115179.pdf
''There are no known familial or genetic TSEs of animals, although polymorphisms in the PRNP gene of some species (sheep for example) may influence the length of the incubation period and occurrence of disease.''
c) The commonest form of CJD occurs as a sporadic disease, the cause of which is unknown, although genetic factors (particularly the codon 129 polymorphism in the prion protein gene (PRNP)) influence disease susceptibility. The familial forms of human TSEs (see Box 1) appear to have a solely genetic origin and are closely associated with mutations or insertions in the PRNP gene. Most, but not all, of the familial forms of human TSEs have been transmitted experimentally to animals. There are no known familial or genetic TSEs of animals, although polymorphisms in the PRNP gene of some species (sheep for example) may influence the length of the incubation period and occurrence of disease.
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/209755/Part_1_-_Introduction.pdf
P-145 Estimating chronic wasting disease resistance in cervids using real time quaking- induced conversion
Nicholas J Haley1, Rachel Rielinqer2, Kristen A Davenport3, W. David Walter4, Katherine I O'Rourke5, Gordon Mitchell6, Juergen A Richt2 1
Our studies demonstrate that in vitro amplification metrics predict in vivo susceptibility, and that alleles with multiple codons, each influencing resistance independently, do not necessarily contribute additively to resistance. Importantly, we found that the white-tailed deer 226K substrate exhibited the slowest amplification rate among those evaluated, suggesting that further investigation of this allele and its resistance in vivo are warranted to determine if absolute resistance to CWD is possible. ***at present, no cervid PrP allele conferring absolute resistance to prion infection has been identified.
PRION 2016 CONFERENCE TOKYO
http://prion2016.org/dl/newsletter_03.pdf
http://chronic-wasting-disease.blogspot.com/2017/04/
***> at present, no PrPC allele conferring absolute resistance in cervids has been identified.
J Gen Virol. 2017 Nov; 98(11): 2882–2892.
Published online 2017 Oct 23. doi: 10.1099/jgv.0.000952
Estimating chronic wasting disease susceptibility in cervids using real-time quaking-induced conversion
Chronic wasting disease (CWD) resistance in cervids is often characterized as decreased prevalence and/or protracted disease progression in individuals with specific alleles; at present, no PrPC allele conferring absolute resistance in cervids has been identified.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845664/pdf/jgv-98-2882.pdf
SUNDAY, MAY 04, 2025
Texas Senate Bill 2651 establishment of a pilot program to breed deer resistant to CWD TSE Prion, what could go wrong?
Texas S.B. 2843 Directs TPWD to conduct a comprehensive study of current measures to control chronic wasting disease (CWD) in deer
Trying to legislate CWD is what got Texas in this CWD mess to begin with, how did that work out$$$ Legislators and Politicians need to stay away and let TPWD and TAHC et try and contain this mess that Legislators and Politicians got us in, imo, called CWD TSE Prion…terry
THURSDAY, MAY 09, 2024
Oklahoma HB3462 Chronic Wasting Disease Genetic Improvement Act and Legislating CWD Science
Indiana trying to legislate and GMO itself from CWD, instead fixing the problems$$$
INDIANA SENATE BILL 32 Prevention of chronic wasting disease. Requires the department of natural resources to establish a pilot program to combat chronic wasting disease in deer
INDIANA SENATE BILL No. 32
DIGEST OF INTRODUCED BILL
Citations Affected: IC 14-22-34.5.
Synopsis: Prevention of chronic wasting disease. Requires the
department of natural resources to establish a pilot program to combat
chronic wasting disease in deer.
Effective: July 1, 2025.
Glick
January 8, 2025, read first time and referred to Committee on Natural Resources.
snip...
Sec. 3. As used in this chapter, "pilot program" means the
chronic wasting disease pilot program established under section 4 of this chapter.
Sec. 4. Not later than December 31, 2025, the department shall establish the chronic wasting disease pilot program to enhance the genetic durability of Indiana's white-tailed deer population.
Sec. 5. The department shall do the following:
(1) Collect DNA samples to establish a baseline of average genetic codon markers and genomic breeding values for native, free-range Indiana white-tailed deer.
(2) Establish a testing location for DNA samples collected from native, free-range Indiana white-tailed deer.
(3) Create andoperate a captive breedingprogramfor native, free-range Indiana white-tailed deer that:
(A) identifies white-tailed deer genetically resistant to chronic wasting disease by assigning white tailed deer a genomically estimated breeding value (GEBV);
(B) breeds the genetically resistant white-tailed deer to increase the population's genetic resistance to chronic wasting disease; and
(C) releases the bred female and male white-tailed deer between February and April 2027.
(4) Take any additional action necessary to establish and operate the pilot program.
Sec. 6.(a) The department may sell white-tailed deer bred from the pilot program for five hundred dollars ($500) per deer.
(b) The departmentshall notsell more than fifty percent (50%) of the bred white-tailed deer from the pilot program.
Sec. 7. Funds collected from the sale of white-tailed deer bred from the pilot program shall be deposited in the fish and wildlife fund.
Sec. 8. The department may adopt rules under IC 4-22-2 to implement this chapter.
Sec. 9. This chapter expires January 1, 2028.
Votes
Status
Spectrum: Partisan Bill (Republican 1-0)
Status: Introduced on January 8 2025 - 25% progression
Action: 2025-01-08 - First reading: referred to Committee on Natural Resources
Pending: Senate Natural Resources Committee
Hearing: Jan 13 @ 2:30 pm in Room 130
Text: Latest bill text (Introduced) [PDF]
Summary
Prevention of chronic wasting disease. Requires the department of natural resources to establish a pilot program to combat chronic wasting disease in deer.
Research
playing with fire imo...terry
“If slower disease progression results in longer-lived, infected deer with longer periods of infectiousness, resistance may lead to increased disease transmission rates, higher prion concentrations in the environment, and increased prevalence, as has been observed in some captive deer herds (Miller et al., 2006; Keane et al., 2008a).”
FRIDAY, FEBRUARY 21, 2025
Indiana Second positive case of chronic wasting disease confirmed
LEGISLATING CWD TSE Prion, Bills to release Genetically Modified Cervid into the wild, what could go wrong?
“If slower disease progression results in longer-lived, infected deer with longer periods of infectiousness, resistance may lead to increased disease transmission rates, higher prion concentrations in the environment, and increased prevalence, as has been observed in some captive deer herds (Miller et al., 2006; Keane et al., 2008a).”
Genetic susceptibility to chronic wasting disease in free-ranging white-tailed deer: Complement component C1q and Prnp polymorphisms§
Julie A. Blanchong a, *, Dennis M. Heisey b , Kim T. Scribner c , Scot V. Libants d , Chad Johnson e , Judd M. Aiken e , Julia A. Langenberg f , Michael D. Samuel g
snip...
Identifying the genetic basis for heterogeneity in disease susceptibility or progression can improve our understanding of individual variation in disease susceptibility in both free-ranging and captive populations. What this individual variation in disease susceptibility means for the trajectory of disease in a population, however, is not straightforward. For example, the greater, but not complete, resistance to CWD in deer with at least one Serine (S) at amino acid 96 of the Prnp gene appears to be associated with slower progression of disease (e.g., Johnson et al., 2006; Keane et al., 2008a). If slower disease progression results in longer-lived, infected deer with longer periods of infectiousness, resistance may lead to increased disease transmission rates, higher prion concentrations in the environment, and increased prevalence, as has been observed in some captive deer herds (Miller et al., 2006; Keane et al., 2008a). Alternatively, if the slower progression of disease in resistant deer is not associated with longer periods of infectiousness, but might instead indicate a higher dose of PrPCWD is required for infection, transmission rates in the population could decline especially if, as in Wisconsin, deer suffer high rates of mortality from other sources (e.g., hunting). Clearly, determining the relationship between genetic susceptibility to infection, dose requirements, disease progression, and the period of PrPCWD infectiousness are key components for understanding the consequences of CWD to free-ranging populations.
Volume 30, Number 10—October 2024
Research
Temporal Characterization of Prion Shedding in Secreta of White-Tailed Deer in Longitudinal Study of Chronic Wasting Disease, United States
Our findings suggest that deer expressing alternative PRNP polymorphisms might live longer and, although they shed fewer prions throughout CWD course, might over their extended lifespan increase CWD prions in the environment
Looks like another game of TSE Prion Poker is about to play out $$$
CWD Status Captive Herds
re-Deer farmers want to use genetics to address chronic wasting disease in Senate bill 32
Greetings WFYI et al
be very careful playing with mother nature, and making CWD last longer in cervids, thus, longer shedding of CWD into the environment, that could come back 10 fold. once the TSE Prion CWD GENIE is out of the bottle, you can't put it back in.
please let me elaborate on all this. it's long, but i think you all might be enlightened a bit on the whole mess, i.e. Transmission Spongiform Encephalopathy TSE Prion disease. hope so anyway.
i hope you find this information useful.
warmest regards, terry
re-Deer farmers want to use genetics to address chronic wasting disease in Senate bill
***> at present, no PrPC allele conferring absolute resistance in cervids has been identified.
***> “If slower disease progression results in longer-lived, infected deer with longer periods of infectiousness, resistance may lead to increased disease transmission rates, higher prion concentrations in the environment, and increased prevalence, as has been observed in some captive deer herds (Miller et al., 2006; Keane et al., 2008a).”
snip…end
THURSDAY, APRIL 24, 2025
***> US Captive CWD Positive Herds Update April 2025
terry
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