# Rabbits, Dogs, Horses - Resistant

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#### Mike

##### Well-known member
Of course "Flipper" doesn't want you to know it, but a simple "salt bridge" may be a key ingredient towards resistance and/or cure.

The nature of the infectious agents: PrP models of resistant species to prion diseases (dog, rabbit and horses)

Jiapu Zhang

(Submitted on 23 Jun 2011)

Prion diseases are invariably fatal and highly infectious neurodegenerative diseases affecting humans and animals. By now there have not been some effective therapeutic approaches to treat all these prion diseases. In 2008, canine mammals including dogs (canis familials) were the first time academically reported to be resistant to prion diseases (Vaccine 26: 2601--2614 (2008)). Rabbits are the mammalian species known to be resistant to infection from prion diseases from other species (Journal of Virology 77: 2003--2009 (2003)). Horses were reported to be resistant to prion diseases too (Proceedings of the National Academy of Sciences USA 107: 19808--19813 (2010)). By now all the NMR structures of dog, rabbit and horse prion proteins had been released into protein data bank respectively in 2005, 2007 and 2010 (Proceedings of the National Academy of Sciences USA 102: 640--645 (2005), Journal of Biomolecular NMR 38:181 (2007), Journal of Molecular Biology 400: 121--128 (2010)). Thus, at this moment it is very worth studying the NMR molecular structures of horse, dog and rabbit prion proteins to obtain insights into their immunity prion diseases.
This article reports the findings of the molecular structural dynamics of wild-type horse, dog, and rabbit prion proteins. The dog and horse prion proteins have stable molecular structures whether under neutral or low pH environments. Rabbit prion protein has been found having stable molecular structures under neutral pH environment, but without structural stability under low pH environment. Under low pH environment, the salt bridges such as D177--R163 were broken and caused the collapse of the stable $\alpha$-helical molecular structures.

This paper is an Invited Book Chapter for "Prions and Prion Diseases: New Developments (J.M. Verdier Eds.), NOVA Publishers, 2011."

Subjects:

Biomolecules (q-bio.BM); Biological Physics (physics.bio-ph)

Cite as:

arXiv:1106.4628v1 [q-bio.BM]

#### flounder

##### Well-known member
Mike said:
Of course "Flipper" doesn't want you to know it, but a simple "salt bridge" may be a key ingredient towards resistance and/or cure.

The nature of the infectious agents: PrP models of resistant species to prion diseases (dog, rabbit and horses)

Jiapu Zhang

(Submitted on 23 Jun 2011)

Prion diseases are invariably fatal and highly infectious neurodegenerative diseases affecting humans and animals. By now there have not been some effective therapeutic approaches to treat all these prion diseases. In 2008, canine mammals including dogs (canis familials) were the first time academically reported to be resistant to prion diseases (Vaccine 26: 2601--2614 (2008)). Rabbits are the mammalian species known to be resistant to infection from prion diseases from other species (Journal of Virology 77: 2003--2009 (2003)). Horses were reported to be resistant to prion diseases too (Proceedings of the National Academy of Sciences USA 107: 19808--19813 (2010)). By now all the NMR structures of dog, rabbit and horse prion proteins had been released into protein data bank respectively in 2005, 2007 and 2010 (Proceedings of the National Academy of Sciences USA 102: 640--645 (2005), Journal of Biomolecular NMR 38:181 (2007), Journal of Molecular Biology 400: 121--128 (2010)). Thus, at this moment it is very worth studying the NMR molecular structures of horse, dog and rabbit prion proteins to obtain insights into their immunity prion diseases.
This article reports the findings of the molecular structural dynamics of wild-type horse, dog, and rabbit prion proteins. The dog and horse prion proteins have stable molecular structures whether under neutral or low pH environments. Rabbit prion protein has been found having stable molecular structures under neutral pH environment, but without structural stability under low pH environment. Under low pH environment, the salt bridges such as D177--R163 were broken and caused the collapse of the stable $\alpha$-helical molecular structures.

This paper is an Invited Book Chapter for "Prions and Prion Diseases: New Developments (J.M. Verdier Eds.), NOVA Publishers, 2011."

Subjects:

Biomolecules (q-bio.BM); Biological Physics (physics.bio-ph)

Cite as:

arXiv:1106.4628v1 [q-bio.BM]

i dream of miracles too happening some day, but until resistance is proven mike, why jump for joy?

mike old buddy, your gonna have to get up earlier than that.

Bradley et al stated long ago ;

"I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough."

I remember they said this about those Classic Scrapie in Sheep with the ARR/ARR Prion Genotype too. what happened there mike ???

We report the identifi cation of 2 natural scrapie cases in ARR/ARR sheep that have biochemical and transmission characteristics similar to cases of classic scrapie, although the abnormally folded prion protein (PrPSc) was associated with a lower proteinase-K resistance. PrPSc was clearly distinct from BSE prions passaged in sheep and from atypical scrapie prions. These fi ndings strongly support the idea that scrapie prions are a mosaic of agents, which harbor different biologic properties, rather than a unique entity....

http://www.cdc.gov/eid/content/13/8/pdfs/1201.pdf

they thought similar thoughts about the Nor-98 atypical scrapie, until transmission studies there proved them wrong as well ;

-- Communicated by: Terry S Singeltary Sr <[email protected]>

[Although atypical scrapie is not yet ruled out, it is important to realize this is a type of scrapie that thus far has only tended to appear as a sporadic condition in older animals. Currently it has not been shown to follow the same genetic tendencies for propagation as the usual scrapie.

However, the atypical phenotypic appearance has been shown to be preserved on experimental passage.

Atypical scrapie was first identified in Norwegian sheep in 1998 and has subsequently been identified in many countries, as Australia may join that list. It is likely that this case will be sent to the UK for definitive conformation.

[Ref: M Simmons, T Konold, L Thurston, et al. BMC Veterinary Research 2010, 6:14 [provisional abstract available at <http://www.biomedcentral.com/1746-6148/6/14/abstract>]

"Background ----------- "Retrospective studies have identified cases predating the initial identification of this form of scrapie, and epidemiological studies have indicated that it does not conform to the behaviour of an infectious disease, giving rise to the hypothesis that it represents spontaneous disease. However, atypical scrapie isolates have been shown to be infectious experimentally, through intracerebral inoculation in transgenic mice and sheep. [Many of the neurological diseases can be transmitted by intracerebral inoculation, which causes this moderator to approach intracerebral studies as a tool for study, but not necessarily as a direct indication of transmissibility of natural diseases. - Mod.TG]

"The 1st successful challenge of a sheep with 'field' atypical scrapie from an homologous donor sheep was reported in 2007.

"Results -------- "This study demonstrates that atypical scrapie has distinct clinical, pathological, and biochemical characteristics which are maintained on transmission and sub-passage, and which are distinct from other strains of transmissible spongiform encephalopathies in the same host genotype.

"Conclusions ------------ Atypical scrapie is consistently transmissible within AHQ homozygous sheep, and the disease phenotype is preserved on sub-passage."

Lastly, this moderator wishes to thank Terry Singletary for some of his behind the scenes work of providing citations and references for this posting. - Mod.TG]

The HealthMap/ProMED-mail interactive map of Australia is available at <http://healthmap.org/r/00co>. - Sr.Tech.Ed.MJ]

http://www.promedmail.org/pls/otn/f?p=2400:1001:57555::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,81729

TSE in dogs have not been documented simply because OF THE ONLY STUDY, those brain tissue samples were screwed up too. see my investigation of this here, and to follow, later follow up, a letter from defra, AND SEE SUSPICIOUS BRAIN TISSUE SAF's. ...TSS

TSE & HOUNDS

GAH WELLS (very important statement here...TSS)

HOUND STUDY

AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.

http://web.archive.org/web/20010305222642/www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf

76 pages on hound study;

http://web.archive.org/web/20030327022236/http://www.bseinquiry.gov.uk/files/sc/seac16/tab04.pdf

I thought that in Britain dogs had contracted BSE, but perhaps not.

not so fast here;

The spongiform changes were not pathognomonic (ie. conclusive proof) for prion disease, as they were atypical, being largely present in white matter rather than grey matter in the brain and spinal cord. However, Tony Scott, then head of electron microscopy work on TSEs, had no doubt that these SAFs were genuine and that these hounds therefore must have had a scrapie-like disease. I reviewed all the sections myself (original notes appended) and although the pathology was not typical, I could not exclude the possibility that this was a scrapie-like disorder, as white matter vacuolation is seen in TSEs and Wallerian degeneration was also present in the white matter of the hounds, another feature of scrapie.

38.I reviewed the literature on hound neuropathology, and discovered that micrographs and descriptive neuropathology from papers on 'hound ataxia' mirrored those in material from Robert Higgins' hound survey. Dr Tony Palmer (Cambridge) had done much of this work, and I obtained original sections from hound ataxia cases from him. This enabled me provisionally to conclude that Robert Higgins had in all probability detected hound ataxia, but also that hound ataxia itself was possibly a TSE. Gerald Wells confirmed in 'blind' examination of single restricted microscopic fields that there was no distinction between the white matter vacuolation present in BSE and scrapie cases, and that occurring in hound ataxia and the hound survey cases.

39.Hound ataxia had reportedly been occurring since the 1930's, and a known risk factor for its development was the feeding to hounds of downer cows, and particularly bovine offal. Circumstantial evidence suggests that bovine offal may also be causal in FSE, and TME in mink. Despite the inconclusive nature of the neuropathology, it was clearly evident that this putative canine spongiform encephalopathy merited further investigation.

40.The inconclusive results in hounds were never confirmed, nor was the link with hound ataxia pursued. I telephoned Robert Higgins six years after he first sent the slides to CVL. I was informed that despite his submitting a yearly report to the CVO including the suggestion that the hound work be continued, no further work had been done since 1991. This was surprising, to say the very least.

41.The hound work could have provided valuable evidence that a scrapie-like agent may have been present in cattle offal long before the BSE epidemic was recognised. The MAFF hound survey remains unpublished.

Histopathological support to various other published MAFF experiments

42.These included neuropathological examination of material from experiments studying the attempted transmission of BSE to chickens and pigs (CVL 1991) and to mice (RVC 1994).

http://www.bseinquiry.gov.uk/witness/htm/stat067.htm

It was thought likely that at least some, and probably all, of the cases in zoo animals were caused by the BSE agent. Strong support for this hypothesis came from the findings of Bruce and others (1994) ( Bruce, M.E., Chree, A., McConnell, I., Foster, J., Pearson, G. & Fraser, H. (1994) Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and species barrier. Philosophical Transactions of the Royal Society B 343, 405-411: J/PTRSL/343/405 ), who demonstrated that the pattern of variation in incubation period and lesion profile in six strains of mice inoculated with brain homogenates from an affected kudu and the nyala, was similar to that seen when this panel of mouse strains was inoculated with brain from cattle with BSE. The affected zoo bovids were all from herds that were exposed to feeds that were likely to have contained contaminated ruminant-derived protein and the zoo felids had been exposed, if only occasionally in some cases, to tissues from cattle unfit for human consumption.

snip...

http://collections.europarchive.org/tna/20080102174910/http://www.bseinquiry.gov.uk/files/ws/s324.pdf

2005

DEFRA Department for Environment, Food & Rural Affairs

Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk

GTN: FAX:

Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518

21 November 2001

Dear Mr Singeltary

TSE IN HOUNDS

Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.

As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.

Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.

Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less

critical. For more details see- page 8

http://web.archive.org/web/20041113122320/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf

As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address.

Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK

You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any suspect SE in dogs for further investigation. To date there has never been positive identification of a TSE in a dog.

Yours sincerely 4

HUGH MCDONAGH BSE CORRESPONDENCE SECTION

======================================

IN CONFIDENCE

SUSPECT BSE IN A HORSE

CYO BSE 1 9

IN CONFIDENCE

SUSPECT BSE IN A HORSE

The Parliamentary Secretary (Mr Maclean) will wish to be aware that, in making his differential diagnosis, a veterinary surgeon in the Reading area has included the possibility of BSE in a horse under his care. Although it is unlikely to be BSE, because of the symptoms exhibited the veterinarian believes that he cannot exclude the possibility. The case was brought to the notice of one of the veterinary staff at the CVL by the owner's veterinary surgeon and liaison is being maintained.

The horse in question is a five-year old eventing gelding which was purchased by the present owner about four months ago. Approximately two months after purchase the animal became a little apprehensive, developed mild nervous symptoms and became over-sensitive to noise. The nervous symptoms have increased and the horse is now practically impossible to ride. Investigations by the owner's private veterinary surgeon are continuing but it is likely that the animal will have to be destroyed.

If the horse should die or be destroyed, a full post-mortem examination will be required for insurance purposes and will probably be carried out at a non-Ministry laboratory. However, Mr Bradley of the Pathology Department, CVL, has informed the private veterinary surgeon that he is willing to provide a second opinion on the brain histology if requested.

I will keep the Parliamentary Secretary informed of any further developments in the case.

I CRAWFORD

14 May 1990

Mr M P H Hill, PS/Parliamentary secretary (Mr Maclean) - by FAX

cc:

Private Offices

Mr K C Meldrum

Mrs E A J Attridge D J Evans Mr K C Taylor Mr R Lawson Mr R Bradley. CVL

(hand written notes i cannot read all (cut short) as follows...tss)

The Parliamentary Secretary (Mr Maclean was grateful for this. He said that we must keep very close to ...on it, and when the horse dies, or is put down we must be told immediately. He also feels it is very important that our veterinary staff be involved in the brain examination. .........(cannot read the rest .............TSS)

90/05.14/10.1

http://collections.europarchive.org/tna/20080102214337/http://www.bseinquiry.gov.uk/files/yb/1990/05/14010001.pdf

1. Mr G S Podmore

PS/Secretary of State

cc PS/Permanent Secretary Mr .T W Preston Mr .T I Davies Mr D R Williams Mr D Summers

POSSIBLE SPONGIFORM ENCEPHALOPATHY IN A HORSE

You will wish to be aware that I have just received a note from Mr D Summers, the DRVO, that a possible case of a Spongiform Encephalopathy (SE) has been reported in a horse in the Brecon area.

The local veterinary surgeon reported yesterday afternoon a suspicion that a horse had contracted SE as it was showing clinical- symptoms similar to those described in cattle suffering from BSE. By yesterday evening the horse was in a comatose state and on humane grounds was destroyed by the veterinary surgeon.

At his request a full post mortem and a laboratory investigation will be started at the Carmarthen Veterinary Investigation Centre this morning in an attempt to ascertain the exact course. This will probably take at least 2 weeks. Charges to the veterinary surgeon have been waived in this instance.

Points particularly mentioned by the veterinary surgeon about this case were that the premises had an apparently similar case in another of their horses, several months ago; and that the horses had been fed cattle cake. Clearly. in his mind, there is a suspicion of a link with BSE; It must be emphasised. however, that at present we cannot even be certain that an SE of any sort is involved. These events are not exactly confidential but clearly no one is anxious to go out of their way to publicise them.

Any further information will be passed on as soon as it is available.

26th June 1990

Note by The BSE Inquiry Secretariat The attached document may now be found at the following locations 90/06.26/10-1

90/06.26/9.1

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1990/06/26009001.pdf

Mr A Huws Principal WOAD2A CP2

SUSPECT BSE IN A HORSE

You will wish to be aware that on Thursday afternoon 25 June the T/DVO Powys received a phone call from a veterinary Surgeon reporting his suspicion that a horse had contracted BSE after having been fed cattle cake. The clinical symptoms described were similar to those shown by cattle there being a similar case some months ago on the same premises.

The owner' s name and address is:

Irene Thomas J Thomas & Company Riding Stables Penybryn Llangorse Brecon

The horse is a 12 year old gelding used for pony trekking.

By yesterday evening the horse was in a comatose state and on humane grounds was destroyed by the veterinary Surgeon. At his request a full post mortem and laboratory investigation will be carried out at the Carmarthen Veterinary Investigation Centre this morning to ascertain the exact cause; I have been told this will take at least two weeks. Charges to the veterinary Surgeon have been waived in this instance.

I will inform you immediately I receive a diagnosis.

26 June 1990

D SUMMERS DRVO

cc

Mr D R Williams, RVO

Mr A R Hunter, SVIO

90/06.26/10.1

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1990/06/26010001.pdf

Greetings,

PLEASE NOTE, TWO WEEKS, TWO MONTHS, TWO YEARS, TWO DECADES PASSED, AND NO OTHER MENTION OF THE CASE OF BSE TO HORSE WAS EVER MENTIONED AGAIN, that I could find. The above links were the last ever mentioned of these suspect cases of BSE in Horses, and the pathology reports there from were never furnished. SO, in my opinion, since the silence was so deafening, the BSE case to HORSE must have been positive, or they would have proudly displayed the pathology report negating the BSE positive in the Horse.

NOW, why could this be \$

IN CONFIDENCE

reference...

RB3.20

TRANSMISSION TO CHIMPANZEES

1. Kuru and CJD have been successfully transmitted to chimpanzees but scrapie and TME have not.

2. We cannot say that scrapie will not transmit to chimpanzees. There are several scrapie strains and I am not aware that all have been tried (that would have to be from mouse passaged material). Nor has a wide enough range of field isolates subsequently strain typed in mice been inoculated by the appropriate routes (i/c, ilp and i/v) :

3. I believe the proposed experiment to determine transmissibility, if conducted, would only show the susceptibility or resistance of the chimpanzee to infection/disease by the routes used and the result could not be interpreted for the predictability of the susceptibility for man. Proposals for prolonged oral exposure of chimpanzees to milk from cattle were suggested a long while ago and rejected.

4. In view of Dr Gibbs' probable use of chimpazees Mr Wells' comments (enclosed) are pertinent. I have yet to receive a direct communication from Dr Schellekers but before any collaboration or provision of material we should identify the Gibbs' proposals and objectives.

5. A positive result from a chimpanzee challenged severely would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

6. A negative result would take a lifetime to determine but that would be a shorter period than might be available for human exposure and it would still not answer the question regarding mans' susceptibility. In the meantime no doubt the negativity would be used defensively. It would however be counterproductive if the experiment finally became positive. We may learn more about public reactions following next Monday' s meeting.

23 September 1990

Dr T W A Little

Dr B J Shreeve

90/9.23/1.1.

http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

tss

#### hopalong

##### Well-known member
As usuall, a lot of IFS, perhaps, could be's. I thinks, simuilar,etc in all of your statements Terry(the sky is falling ) Singltary :roll: