Volume 31, Number 5—May 2025
Dispatch
Administration of L-type Bovine Spongiform Encephalopathy to Macaques to Evaluate Zoonotic Potential
Abstract
We administered L-type bovine spongiform encephalopathy prions to macaques to determine their potential for transmission to humans. After 75 months, no clinical symptoms appeared, and prions were undetectable in any tissue by Western blot or immunohistochemistry. Protein misfolding cyclic amplification, however, revealed prions in the nerve and lymphoid tissues.
Conclusion
We noted no detectable evidence of PrPSc by WB or IHC in any tissues of L-BSE orally inoculated macaques. Nevertheless, PMCA successfully amplified PrPres from lymphatic and neural tissues. The PrPres exhibited electrophoretic patterns distinct from those detected by PMCA using L-BSE–affected cattle BH as the seed (Figure 3, panel C), indicating that the PrPSc used as the template for PrPres amplification in orally inoculated macaques did not originate from the bovine L-BSE prions used as inoculum. Instead, PrPSc were newly generated by the conversion of macaque PrPC by bovine L-BSE prions. Our results provide strong evidence that L-BSE can infect macaques via the oral route.
We found no evidence that PrPSc reached the brain in orally inoculated macaques; however, the macaques euthanized 6 years postinoculation might have been in the preclinical period. At low infection levels, lymph nodes play a vital role in prion spread to the central nervous system (11). Therefore, had the macaques been maintained for a longer period, they might have developed prion disease. Retrospective surveillance studies using the appendix and tonsil tissues suggested a considerable number of humans harboring vCJD in a carrier state (12). Thus, we cannot exclude that L-BSE orally inoculated macaques could similarly remain in a potentially infectious state.
The brain of L-BSE intracerebrally inoculated macaque accumulated prions with biochemical properties resembling bovine L-BSE prions (Figure 3, panel C; Appendix Figure 2); however, we observed no PrPSc accumulation in lymphoid tissues by WB or IHC (4). In contrast, macaques orally inoculated with C-BSE prions showed PrPSc accumulation in lymphoid tissues, including the spleen, tonsils, and mesenteric lymph nodes by WB and IHC (13). In our study, L-BSE orally inoculated macaques harbored C-BSE–like prions in their lymphoid and neural tissues. Interspecies transmission of L-BSE prions to ovine PrP transgenic mice can result in a shift toward C-BSE–like properties (14,15). Our data suggest that L-BSE prions may alter biophysical and biochemical properties, depending on interspecies transmission and inoculation route, acquiring traits similar to those of C-BSE prions. This transformation might result from structural changes in the L-BSE prion to C-BSE–like prions and other lymphotropic prions within lymphoid tissues or from the selective propagation of low-level lymphotropic substrains within the L-BSE prion population.
The first limitation of our study is that the oral inoculation experiment involved only 2 macaques and tissues collected at 6 years postinoculation, before disease onset. Consequently, subsequent progression of prion disease symptoms remains speculative. A larger sample size and extended observation periods are required to conclusively establish infection in orally inoculated macaques. Furthermore, we performed no bioassays for PMCA-positive samples, leaving the relationship between PMCA results and infectious titers undefined. Considering that PrPres amplifications from tissues from the orally inoculated macaque tissues required 2 rounds of PMCA, the PrPSc levels in positive tissues might have been extremely low and undetectable in the bioassay.
Snip…
Previous studies have demonstrated that L-BSE can be orally transmitted to cattle (7) and might have caused prion disease in farm-raised minks (6), indicating that L-BSE could naturally affect various animal species.
Our findings suggest that L-BSE can also be orally transmitted to macaques. Therefore, current control measures aimed at preventing primary C-BSE in cattle and humans may also need to consider the potential risk of spontaneous L-BSE transmission.
References…snip…end
wwwnc.cdc.gov
***> Our results provide strong evidence that L-BSE can infect macaques via the oral route.
Wednesday, May 24, 2023
***> WAHIS, WOAH, OIE, United States of America Bovine spongiform encephalopathy Immediate notification
wahis.woah.org
woahoie.blogspot.com
prpsc.proboards.com
SATURDAY, MAY 20, 2023
***> Tennessee State Veterinarian Alerts Cattle Owners to Disease Detection Mad Cow atypical L-Type BSE
prpsc.proboards.com
MAY 19, 2023
2 weeks before the announcement of this recent mad cow case in the USA, i submitted this to the APHIS et al;
***> APPRX. 2 weeks before the recent mad cow case was confirmed in the USA, in Tennessee, atypical L-Type BSE, I submitted this to the APHIS et al;
Document APHIS-2023-0027-0001 BSE Singeltary Comment Submission May 2, 2023
''said 'burden' cost, will be a heavy burden to bear, if we fail with Bovine Spongiform Encephalopathy BSE TSE Prion disease, that is why this information collection is so critical''...
www.regulations.gov
TUESDAY, APRIL 15, 2025
Cases of Creutzfeldt-Jakob disease in young individuals: open questions regarding aetiology
Recently, two young individuals, aged 15 and 21, were diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD) in Canada and the United States, respectively (D'Arcy et al., 2019; Ahn et al., 2024).
www.frontiersin.org
creutzfeldt-jakob-disease.blogspot.com
terry
Dispatch
Administration of L-type Bovine Spongiform Encephalopathy to Macaques to Evaluate Zoonotic Potential
Abstract
We administered L-type bovine spongiform encephalopathy prions to macaques to determine their potential for transmission to humans. After 75 months, no clinical symptoms appeared, and prions were undetectable in any tissue by Western blot or immunohistochemistry. Protein misfolding cyclic amplification, however, revealed prions in the nerve and lymphoid tissues.
Conclusion
We noted no detectable evidence of PrPSc by WB or IHC in any tissues of L-BSE orally inoculated macaques. Nevertheless, PMCA successfully amplified PrPres from lymphatic and neural tissues. The PrPres exhibited electrophoretic patterns distinct from those detected by PMCA using L-BSE–affected cattle BH as the seed (Figure 3, panel C), indicating that the PrPSc used as the template for PrPres amplification in orally inoculated macaques did not originate from the bovine L-BSE prions used as inoculum. Instead, PrPSc were newly generated by the conversion of macaque PrPC by bovine L-BSE prions. Our results provide strong evidence that L-BSE can infect macaques via the oral route.
We found no evidence that PrPSc reached the brain in orally inoculated macaques; however, the macaques euthanized 6 years postinoculation might have been in the preclinical period. At low infection levels, lymph nodes play a vital role in prion spread to the central nervous system (11). Therefore, had the macaques been maintained for a longer period, they might have developed prion disease. Retrospective surveillance studies using the appendix and tonsil tissues suggested a considerable number of humans harboring vCJD in a carrier state (12). Thus, we cannot exclude that L-BSE orally inoculated macaques could similarly remain in a potentially infectious state.
The brain of L-BSE intracerebrally inoculated macaque accumulated prions with biochemical properties resembling bovine L-BSE prions (Figure 3, panel C; Appendix Figure 2); however, we observed no PrPSc accumulation in lymphoid tissues by WB or IHC (4). In contrast, macaques orally inoculated with C-BSE prions showed PrPSc accumulation in lymphoid tissues, including the spleen, tonsils, and mesenteric lymph nodes by WB and IHC (13). In our study, L-BSE orally inoculated macaques harbored C-BSE–like prions in their lymphoid and neural tissues. Interspecies transmission of L-BSE prions to ovine PrP transgenic mice can result in a shift toward C-BSE–like properties (14,15). Our data suggest that L-BSE prions may alter biophysical and biochemical properties, depending on interspecies transmission and inoculation route, acquiring traits similar to those of C-BSE prions. This transformation might result from structural changes in the L-BSE prion to C-BSE–like prions and other lymphotropic prions within lymphoid tissues or from the selective propagation of low-level lymphotropic substrains within the L-BSE prion population.
The first limitation of our study is that the oral inoculation experiment involved only 2 macaques and tissues collected at 6 years postinoculation, before disease onset. Consequently, subsequent progression of prion disease symptoms remains speculative. A larger sample size and extended observation periods are required to conclusively establish infection in orally inoculated macaques. Furthermore, we performed no bioassays for PMCA-positive samples, leaving the relationship between PMCA results and infectious titers undefined. Considering that PrPres amplifications from tissues from the orally inoculated macaque tissues required 2 rounds of PMCA, the PrPSc levels in positive tissues might have been extremely low and undetectable in the bioassay.
Snip…
Previous studies have demonstrated that L-BSE can be orally transmitted to cattle (7) and might have caused prion disease in farm-raised minks (6), indicating that L-BSE could naturally affect various animal species.
Our findings suggest that L-BSE can also be orally transmitted to macaques. Therefore, current control measures aimed at preventing primary C-BSE in cattle and humans may also need to consider the potential risk of spontaneous L-BSE transmission.
References…snip…end
Administration of L-Type Bovine Spongiform Encephalopathy to Macaques to Evaluate Zoonotic Potential
Administration of L-BSE to Macaques
wwwnc.cdc.gov
***> Our results provide strong evidence that L-BSE can infect macaques via the oral route.
Wednesday, May 24, 2023
***> WAHIS, WOAH, OIE, United States of America Bovine spongiform encephalopathy Immediate notification
WAHIS
WAHIS, WOAH, OIE, United States of America Bovine spongiform encephalopathy Immediate notification
OIE-WAHIS OIE World Animal Health Information System
woahoie.blogspot.com
WAHIS, WOAH, OIE, USA, BSE, IMMEDIATE NOTIFICATION | PrPSc Prion TSE BSE SCRAPIE CWD TME CJD FFI GSS
WAHIS, WOAH, OIE, United States of America Bovine spongiform encephalopathy Immediate notification United States of America - Bovine spongiform encephalopathy - Immediate notification GE
SATURDAY, MAY 20, 2023
***> Tennessee State Veterinarian Alerts Cattle Owners to Disease Detection Mad Cow atypical L-Type BSE
Tennessee Veterinarian Alerts Cattle Owners Confirmed BSE | PrPSc Prion TSE BSE SCRAPIE CWD TME CJD FFI GSS
Tennessee State Veterinarian Alerts Cattle Owners to Disease Detection Mad Cow atypical L-Type BSE Friday, May 19, 2023 | 04:12pm NASHVILLE — The Tennessee State Veterinarian is confirming a ca
MAY 19, 2023
2 weeks before the announcement of this recent mad cow case in the USA, i submitted this to the APHIS et al;
***> APPRX. 2 weeks before the recent mad cow case was confirmed in the USA, in Tennessee, atypical L-Type BSE, I submitted this to the APHIS et al;
Document APHIS-2023-0027-0001 BSE Singeltary Comment Submission May 2, 2023
''said 'burden' cost, will be a heavy burden to bear, if we fail with Bovine Spongiform Encephalopathy BSE TSE Prion disease, that is why this information collection is so critical''...
Regulations.gov
TUESDAY, APRIL 15, 2025
Cases of Creutzfeldt-Jakob disease in young individuals: open questions regarding aetiology
Recently, two young individuals, aged 15 and 21, were diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD) in Canada and the United States, respectively (D'Arcy et al., 2019; Ahn et al., 2024).
Frontiers | Cases of Creutzfeldt-Jakob disease in young individuals: open questions regarding aetiology
(patients older than 50) (Boesenberg et al., 2005). The ratio of type 1 to type 2 PrP Sc subtypes, determined based on glycoform ratios and the electrophoret...
www.frontiersin.org
CREUTZFELDT JAKOB DISEASE: Cases of Creutzfeldt-Jakob disease in young individuals: open questions regarding aetiology
terry
