Exploring the possibility of CWD transmission through artificial insemination of semen from CWD positive bucks

 Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies

Location: Virus and Prion Research

Title: Exploring the possibility of CWD transmission through artificial insemination of semen from CWD positive bucks

Author

	Cassmann, Eric
	Greenlee, Justin

Submitted to: North American Deer Farmer Publication Type: Trade Journal Publication Acceptance Date: 7/1/2022 Publication Date: 7/20/2022 Citation: Cassmann, E.D., Greenlee, J.J. 2022. Exploring the possibility of CWD transmission through artificial insemination of semen from CWD positive bucks. North American Deer Farmer. p. 107-109. Interpretive Summary: Technical Abstract: Artificial insemination is a popular method for herd management and reproduction in the cervid farming industry. There are numerous benefits including increased access to superior genetics, convenience, and increased farm revenue. In this article, we summarize the research that is underway to determine if semen from a CWD infected buck can transmit the disease. Some research has already been performed on the reproductive transmission of CWD in cervids. Scientists from Colorado State University used Muntjac deer to demonstrate that CWD positive does could transmit CWD to their fawns (1). In the study, Muntjac does were bred to CWD negative bucks. At the time of breeding, does were either in the early or late stage of CWD infection. Fawns from both doe groups were positive for CWD. More recent laboratory experiments on semen from CWD positive bucks have demonstrated the presence of CWD prions (2). Researchers used an amplification technique called PMCA (protein misfolding cyclic amplification). The technique amplifies low levels of CWD prions to a point where conventional antibody methods can detect them. The caveat to the discovery of CWD prions in semen is that we’re unsure if the amount of CWD prions in semen is biologically relevant. In other words, is the level of CWD prions in semen sufficient to be infectious and cause disease in deer? In our present study, we are trying to answer that question. We obtained semen from a CWD positive buck. The semen was confirmed to be PMCA positive. For the study, we used the transcervical insemination method in three does. As of June 19th, a single fawn was born. Shortly after birth the fawn was separated to prevent environment CWD exposure. We are assessing both the does and the fawn for the development of CWD. The experiment is expected to last several years, and periodic sampling will help monitor progress. A second phase of the study will investigate the absolute susceptibility of white-tailed deer does to CWD after transcervical and/or vaginal exposure to large amounts of CWD prions. We plan to expose two does to brain suspension from a CWD positive deer. These does will also be monitored long term for the development of disease. If these does remain negative, it would indicate that CWD transmission to the dam is highly unlikely via reproductive tract exposure. https://www.ars.usda.gov/research/publications/publication/?seqNo115=395853 TUESDAY, DECEMBER 31, 2019  In Vitro detection of Chronic Wasting Disease (CWD) prions in semen and reproductive tissues of white tailed deer bucks (Odocoileus virginianus  TEXAS CWD, Have you been ThunderStruck, deer semen, straw bred bucks, super ovulation, and the potential TSE Prion connection, what if?  https://chronic-wasting-disease.blogspot.com/2019/12/in-vitro-detection-of-chronic-wasting.html SUNDAY, FEBRUARY 16, 2020  ***> Jerking for Dollars, Are Texas Politicians and Legislators Masturbating Deer For Money, and likely spreading CWD TSE Prion?  https://chronic-wasting-disease.blogspot.com/2020/02/jerking-for-dollars-are-texas.html THURSDAY, JULY 10, 2014 supercalifragilisticexpialidocious or  superovulationcwdtsepriondocious ?  (It was noted with concern that hormone extracts could be manufactured by a  veterinary surgeon for administration to animals under his care without any  Medicines Act Control.) PITUITARY EXTRACT This was used to help cows  super ovulate.  *** This tissue was considered to be of greatest risk of containing BSE  and consequently transmitting the disease. ***  http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf  http://web.archive.org/web/20090718143059/http://www.bseinquiry.gov.uk/ files/yb/1988/06/08011001.pdf http://chronic-wasting-disease.blogspot.com/2014/07/supercalifragilisticexpialidocious-or.html Proposed Amendments to CWD Zone Rules Your opinions and comments have been submitted successfully. Thank you for participating in the TPWD regulatory process. https://tpwd.texas.gov/business/feedback/public_comment/proposals/202208_cwd.phtml THURSDAY, AUGUST 04, 2022  Texas Proposed Amendments to CWD Zone Rules Singeltary Submission https://chronic-wasting-disease.blogspot.com/2022/08/texas-proposed-amendments-to-cwd-zone.html Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004 Singeltary Submission https://www.regulations.gov/comment/APHIS-2021-0004-0002 https://downloads.regulations.gov/APHIS-2021-0004-0002/attachment_1.pdf Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification https://www.regulations.gov/document/APHIS-2018-0011-0003 https://downloads.regulations.gov/APHIS-2018-0011-0003/attachment_1.pdf Texas Chronic Wasting Disease Discovered at a Deer Breeding Facility in Gillespie County Media Contacts: TAHC Communications public_info@tahc.texas.gov, 512.719.0750 TPWD Press Office news@tpwd.texas.gov, 512.389.8030 For Immediate Release September 2, 2022 Chronic Wasting Disease Discovered at a Deer Breeding Facility in Gillespie County AUSTIN, TX – Chronic Wasting Disease (CWD) has been discovered in a deer breeding facility in Gillespie County. The Texas Parks and Wildlife Department (TPWD) and Texas Animal Health Commission (TAHC) are collaboratively working to determine the source and extent of the first positive detection of the disease in this county. After the mortality of a white-tailed deer on the premises was identified, tissue samples from the one-year-old buck were submitted by the deer breeding facility as part of a required CWD surveillance program. The samples were tested at the Texas A&M Veterinary Medical Diagnostic Laboratory (TVMDL) in College Station on August 17 and indicated the presence of CWD. The National Veterinary Services Laboratory in Ames, Iowa confirmed CWD in those tissue samples on August 30. Immediate action has been taken to secure all deer located at the facility and plans to conduct additional CWD investigations are underway. Additionally, other breeding facilities that received deer or shipped deer to this facility, during the last five years, have been identified and placed under movement restrictions.  “Response staff are diligently working to conduct epidemiological investigations, but the nature of the disease makes definitive findings difficult to determine,” said Dr. Andy Schwartz, TAHC State Veterinarian. “The incubation period of CWD can span years creating disease detection and management challenges.” Animal health and wildlife officials will investigate to determine the extent of the disease within the facility and mitigate risks to Texas’ CWD susceptible species. Quick detection of CWD can help mitigate the disease’s spread. “The discovery of CWD in this breeding facility is an unfortunate situation that TPWD and TAHC take very seriously,” said John Silovsky, Wildlife Division Director for TPWD. “Both agencies will respond appropriately to this matter to protect the state’s susceptible species from further disease exposure.” First recognized in 1967 in captive mule deer in Colorado, CWD has since been documented in captive and/or free-ranging deer in 30 states and three Canadian provinces. To date, 376 captive or free-ranging cervids — including white-tailed deer, mule deer, red deer and elk — in 15 Texas counties have tested positive for CWD. For more information on previous detections visit the CWD page on the TPWD website. Testing for CWD allows wildlife biologists and animal health officials to get a clearer picture of the prevalence and distribution of the disease across Texas. Proactive monitoring improves the state’s response time to a CWD detection and can greatly reduce the risk of the disease further spreading to neighboring captive and free-ranging populations. With each discovery of a new CWD positive area in the state, CWD zones are established as a strategy to manage and contain the disease. TPWD officials will be working towards delineating and establishing a new zone in Gillespie County to be implemented later this fall. Hunters in surveillance and containment zones must meet submission requirements of harvested CWD susceptible species. TPWD will be providing additional information to landowners and hunters in Gillespie County regarding CWD sampling locations and options to have their deer tested. Additionally, hunters outside of established surveillance and containment zones are encouraged to voluntarily submit their harvest for testing at a check station, for free, before heading home from the field. A map of TPWD check stations for all CWD zones can be found on the TPWD website. CWD is a fatal neurological disease found in certain cervids, including deer, elk, moose and other members of the deer family. The disease is highly transmissible and can remain infectious on the landscape for several years. If left unmanaged, CWD can have long-term impacts on the native deer herd and local economies. Clinical signs may include progressive weight loss, stumbling or tremors with a lack of coordination, excessive thirst, salivation or urination, loss of appetite, teeth grinding, abnormal head posture and/or drooping ears. These signs may not become evident until long after animals have become infected. Therefore, testing is the best tool available for detecting CWD at an early stage and containing it with appropriate management strategies. To date there is no evidence that CWD poses a risk to humans or non-cervids. However, as a precaution, the U.S. Centers for Disease Control and the World Health Organization recommend not to consume meat from infected animals. For more information about CWD, visit the TPWD web site or the TAHC web site. ### https://www.tahc.texas.gov/news/2022/2022-09-02_CWD-GillespieCo.pdf Texas CWD Count As Of Late August 2022 Totals 376 TPWC Implements Two Year Surveillance Zone Four Counties TPW Commission Implements Two Year Chronic Wasting Disease Surveillance Zone in Four Counties Sept. 1, 2022 Media Contact: TPWD News, Business Hours, 512-389-8030 AUSTIN— A surveillance zone covering almost 200,000 acres in Duval, Jim Wells, Live Oak and McMullen counties will be implemented for two years after feedback was received in the August meeting of the Texas Parks and Wildlife (TPW) Commission. This zone will take effect prior to the 2022-2023 hunting season and TPW commissioners will consider the resulting data presented by Texas Parks and Wildlife Department (TPWD) staff to assess the need for continued surveillance in the established zone. This zone will include land between U.S. Highway 281 to the east, Farm to Market Road 624 to the north and U.S. Highway 59 to the west. The southern border follows a series of roads including County Road 101, Highway 44, County Roads 145, 172, 170, and 120. This zone also includes the cities of Alice and Freer, as well as highways 59, 44, and 281 between the cities and the main body of the surveillance zone. This will provide a legal means for hunters to transport whole carcasses to deer-processing facilities and/or CWD check stations located in those cities rather than having to quarter the carcasses first. As of late August 2022, 376 captive or free-ranging cervids — including white-tailed deer, mule deer, red deer and elk — in 15 Texas counties have tested positive for CWD. First recognized in 1967 in captive mule deer in Colorado, CWD has since been documented in captive and/or free-ranging deer in 30 states and three Canadian provinces. Testing for CWD allows wildlife biologists to get a clearer picture of the presence of the disease statewide. Proactive monitoring improves the state’s response time to a CWD detection and can greatly reduce the risk of the disease spreading to neighboring captive and free-ranging deer populations. Hunters outside of established surveillance and containment zones are encouraged to voluntarily submit their harvest for testing at a check station for free before heading home from the field. A map of TPWD check stations can be found on the TPWD website. CWD is a fatal neurological disease found in certain cervids, including deer, elk, moose and other members of the deer family. The disease is highly contagious, never goes dormant and can remain infectious on the landscape for several years. If left unmanaged, CWD can have long-term impacts on the native deer herd and local economies. Symptoms may not become evident until long after animals have become infected, so testing is the best tool available for detecting CWD at the earliest stage of infection possible and containing it with appropriate management strategies. Clinical signs may include progressive weight loss, stumbling or tremors with a lack of coordination, excessive thirst, salivation or urination, loss of appetite, teeth grinding, abnormal head posture and/or drooping ears. To date there is no evidence that CWD poses a risk to humans or non-cervids. However, as a precaution, the U.S. Centers for Disease Control and the World Health Organization recommend against consuming meat from infected animals. For more information about CWD, visit the TPWD web site or the TAHC web site. https://tpwd.texas.gov/newsmedia/releases/?req=20220901a CWD Positives in Texas CWD Positive Confirmation Date Free Range/Captive County Source Species Sex Age pending Breeder Deer Hunt Facility #9 White-tailed Deer F 3.9 pending Breeder Deer Hunt Facility #9 White-tailed Deer M 1.8 N/A Free Range Hartley N/A Mule Deer M 5.5 2022-05-27 Free Range El Paso N/A Mule Deer M 3.5 2022-05-25 Free Range El Paso N/A Mule Deer M 4.5 2022-04-21 Breeder Release Site Medina Facility #4 White-tailed Deer M 4.5 2022-04-21 Breeder Release Site Medina Facility #4 White-tailed Deer M 4.5 2022-04-07 Free Range El Paso N/A Mule Deer F 4.5 2022-04-07 Free Range Hudspeth N/A Mule Deer M 8.5 2022-02-28 Breeder Deer Hunt Facility #9 White-tailed Deer M 1.9 2022-02-18 Breeder Deer Kimble Facility #6 White-tailed Deer Unknown 3.5 2022-01-25 Free Range Medina N/A White-tailed Deer F 5.5 2022-01-12 Breeder Deer Hunt Facility #9 White-tailed Deer M 1.5 2022-01-12 Breeder Deer Hunt Facility #9 White-tailed Deer F 3.5 2022-01-12 Breeder Release Site Medina Facility #3 Red Deer F 4.5 2022-01-12 Free Range Hartley N/A White-tailed Deer M 3.5 2022-01-12 Free Range Hartley N/A Mule Deer M 5.5 2022-01-12 Free Range Hartley N/A Mule Deer M 4.5 2022-01-12 Free Range Hartley N/A Mule Deer M 5.5 2022-01-12 Free Range Hartley N/A Mule Deer F 3.5 2022-01-12 Breeder Deer Kimble Facility #6 White-tailed Deer Unknown 5.5 2022-01-12 Free Range Hartley N/A Mule Deer M 3.5 2022-01-12 Free Range Hartley N/A Mule Deer M 7.5 2022-01-10 Free Range Medina N/A White-tailed Deer M 4.5 2022-01-10 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.3 2022-01-10 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 5.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 5.4 2022-01-06 Free Range Medina N/A White-tailed Deer M 2.5 2021-12-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4 2021-12-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4 2021-12-13 Free Range Medina N/A White-tailed Deer M 3.5 2021-12-13 Breeder Deer Duval Facility #13 White-tailed Deer F 4.4 Showing 1 to 100 of 369 National CWD Tracking Map snip... see full listing of CWD positives at; https://tpwd.texas.gov/huntwild/wild/diseases/cwd/tracking/ “Regarding the current situation involving CWD in permitted deer breeding facilities, TPWD records indicate that within the last five years, the seven CWD-positive facilities transferred a total of 2,530 deer to 270 locations in 102 counties and eight locations in Mexico (the destinations included 139 deer breeding facilities, 118 release sites, five Deer Management Permit sites, and three nursing facilities).'' ... It is apparent that prior to the recent emergency rules, the CWD detection rules were ineffective at detecting CWD earlier in the deer breeding facilities where it was eventually discovered and had been present for some time; this creates additional concern regarding adequate mitigation of the risk of transferring CWD-positive breeder deer to release sites where released breeder deer come into contact with free-ranging deer... Commission Agenda Item No. 5 Exhibit B DISEASE DETECTION AND RESPONSE RULES PROPOSAL PREAMBLE 1. Introduction.  snip...  A third issue is the accuracy of mortality reporting. Department records indicate that for each of the last five years an average of 26 deer breeders have reported a shared total of 159 escapes. Department records for the same time period indicate an average of 31 breeding facilities reported a shared total of 825 missing deer (deer that department records indicate should be present in the facility, but cannot be located or verified).  https://tpwd.texas.gov/business/feedback/meetings/2022/1104/agenda/item.phtml?item=5 Counties where CWD Exposed Deer were Released, September 2021 https://tpwd.texas.gov/documents/257/CWD-Trace-OutReleaseSites.pdf Number of CWD Exposed Deer Released by County, September 2021 https://tpwd.texas.gov/documents/258/CWD-Trace-OutReleaseSites-NbrDeer.pdf CHRONIC WASTING DISEASE CASESCWD - STATUS OF CAPTIVE HERDS Updated July 2022 https://www.aphis.usda.gov/animal_health/animal_diseases/cwd/downloads/status-of-captive-herds.pdf PRICE OF CWD TSE PRP POKER GOES UP, WHO'S ALL IN$$$ just out! Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD Samia Hannaoui1 · Irina Zemlyankina1 · Sheng Chun Chang1 · Maria Immaculata Arifn1 · Vincent Béringue2 · Debbie McKenzie3 · Hermann M. Schatzl1 · Sabine Gilch1 Received: 24 May 2022 / Revised: 5 August 2022 / Accepted: 7 August 2022 © The Author(s) 2022 Abstract Prions cause infectious and fatal neurodegenerative diseases in mammals. Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we provide evidence for a zoonotic potential of CWD prions, and its probable signature using mice expressing human prion protein (PrP) as an infection model. Inoculation of these mice with deer CWD isolates resulted in atypical clinical manifestation with prion seeding activity and efficient transmissible infectivity in the brain and, remarkably, in feces, but without classical neuropathological or Western blot appearances of prion diseases. Intriguingly, the protease-resistant PrP in the brain resembled that found in a familial human prion disease and was transmissible upon second passage. Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management. Keywords Chronic wasting disease · CWD · Zoonotic potential · Prion strains · Zoonotic prions HIGHLIGHTS OF THIS STUDY ================================ Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management. In this study, we evaluated the zoonotic potential of CWD using a transgenic mouse model overexpressing human M129-PrPC (tg650 [12]). We inoculated tg650 mice intracerebrally with two deer CWD isolates, Wisc-1 and 116AG [22, 23, 27, 29]. We demonstrate that this transgenic line was susceptible to infection with CWD prions and displayed a distinct leading clinical sign, an atypical PrPSc signature and unusual fecal shedding of infectious prions. Importantly, these prions generated by the human PrP transgenic mice were transmissible upon passage. Our results are the first evidence of a zoonotic risk of CWD when using one of the most common CWD strains, Wisc-1/CWD1 for infection. We demonstrated in a human transgenic mouse model that the species barrier for transmission of CWD to humans is not absolute. The fact that its signature was not typical raises the questions whether CWD would manifest in humans as a subclinical infection, whether it would arise through direct or indirect transmission including an intermediate host, or a silent to uncovered human-to-human transmission, and whether current detection techniques will be sufficient to unveil its presence. Our findings strongly suggest that CWD should be regarded as an actual public health risk. Here, we use humanized mice to show that CWD prions can cross the species barrier to humans, and remarkably, infectious prions can be excreted in feces. Our results indicate that if CWD crosses the species-barrier to humans, it is unlikely to resemble the most common forms of human prion diseases with respect to clinical signs, tissue tropism and PrPSc signature. For instance, PrPSc in variable protease-sensitive prionopathy (VPSPr), a sporadic form of human prion disease, and in the genetic form Gerstmann-Sträussler-Scheinker syndrome (GSS) is defined by an atypical PK-resistant PrPSc fragment that is non-glycosylated and truncated at both C- and N-termini, with a molecular weight between 6 and 8 kDa [24, 44–46]. These biochemical features are unique and distinctive from PrPSc (PrP27-30) found in most other human or animal prion disease. The atypical PrPSc signature detected in brain homogenate of tg650 mice #321 (1st passage) and #3063 (2nd passage), and the 7–8 kDa fragment (Figs. 2, 4) are very similar to that of GSS, both in terms of migration profile and the N-terminal cleavage site. CWD in humans might remain subclinical but with PrPSc deposits in the brain with an unusual morphology that does not resemble the patterns usually seen in different prion diseases (e.g., mouse #328; Fig. 3), clinical with untraceable abnormal PrP (e.g., mouse #327) but still transmissible and uncovered upon subsequent passage (e.g., mouse #3063; Fig. 4), or prions have other reservoirs than the usual ones, hence the presence of infectivity in feces (e.g., mouse #327) suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable. suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable. These findings have strong implications for public health and CWD management. ================================= Supplementary Information The online version contains supplementary material available at  https://doi.org/10.1007/s00401-022-02482-9 snip...see full text; https://link.springer.com/article/10.1007/s00401-022-02482-9 https://link.springer.com/content/pdf/10.1007/s00401-022-02482-9.pdf EFSA Panel on Biological Hazards (BIOHAZ) Antonia Ricci Ana Allende Declan Bolton Marianne Chemaly Robert Davies Pablo Salvador Fernández Escámez ... See all authors  First published: 17 January 2018 https://doi.org/10.2903/j.efsa.2018.5132 also, see;  8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data.  ***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison.  https://efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5132 Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿  Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.  http://jvi.asm.org/content/83/18/9608.full  Prions in Skeletal Muscles of Deer with Chronic Wasting Disease  Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.  http://science.sciencemag.org/content/311/5764/1117..long  Research Paper Cellular prion protein distribution in the vomeronasal organ, parotid, and scent glands of white-tailed deer and mule deer Anthony Ness, Aradhana Jacob, Kelsey Saboraki, Alicia Otero, Danielle Gushue, Diana Martinez Moreno, Melanie de Peña, Xinli Tang, Judd Aiken, Susan Lingle & Debbie McKenzieORCID Icon show less Pages 40-57 | Received 03 Feb 2022, Accepted 13 May 2022, Published online: 29 May 2022 Download citation https://doi.org/10.1080/19336896.2022.2079888 ABSTRACT Chronic wasting disease (CWD) is a contagious and fatal transmissible spongiform encephalopathy affecting species of the cervidae family. CWD has an expanding geographic range and complex, poorly understood transmission mechanics. CWD is disproportionately prevalent in wild male mule deer and male white-tailed deer. Sex and species influences on CWD prevalence have been hypothesized to be related to animal behaviours that involve deer facial and body exocrine glands. Understanding CWD transmission potential requires a foundational knowledge of the cellular prion protein (PrPC) in glands associated with cervid behaviours. In this study, we characterized the presence and distribution of PrPC in six integumentary and two non-integumentary tissues of hunter-harvested mule deer (Odocoileus hemionus) and white-tailed deer (O. virginianus). We report that white-tailed deer expressed significantly more PrPC than their mule deer in the parotid, metatarsal, and interdigital glands. Females expressed more PrPC than males in the forehead and preorbital glands. The distribution of PrPC within the integumentary exocrine glands of the face and legs were localized to glandular cells, hair follicles, epidermis, and immune cell infiltrates. All tissues examined expressed sufficient quantities of PrPC to serve as possible sites of prion initial infection, propagation, and shedding. https://www.tandfonline.com/doi/full/10.1080/19336896.2022.2079888 TUESDAY, AUGUST 23, 2022  Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD These findings have strong implications for public health and CWD management. snip...see full text; https://link.springer.com/article/10.1007/s00401-022-02482-9 https://link.springer.com/content/pdf/10.1007/s00401-022-02482-9.pdf Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD https://chronic-wasting-disease.blogspot.com/2022/08/transmission-of-cervid-prions-to.html Thursday, October 28, 2021  Chronic Wasting Disease (CWD) TSE Prion Zoonosis, friendly fire, iatrogenic transmission, blood products, sporadic CJD, what if? https://itseprion.blogspot.com/2021/10/chronic-wasting-disease-cwd-tse-prion.html THURSDAY, SEPTEMBER 01, 2022  Texas CWD Count As Of Late August 2022 Totals 376 TPWC Implements Two Year Surveillance Zone Four Counties https://chronic-wasting-disease.blogspot.com/2022/09/texas-cwd-count-as-of-late-august-2022.html Terry S. Singeltary Sr.