Susceptibility of cats to prion disease

April 22, 2014

Stewart P, Campbell L, Skogtvedt S, et al. Genetic predictions of prion disease susceptibility in carnivore species based on variability of the prion gene coding region. PLoS One 2012;7:e50623 [free, full text]

Prions are unusual infectious agents made of protein but they are not considered to be living organisms. They are associated with neurodegenerative diseases in various animals, such as bovine spongiform encephalopathy (BSE or “mad cow disease”), feline spongiform encephalopathy (FSE), and Creutzfeldt-Jakob disease in people. All prion diseases are caused by the prion protein, PrP.
 
Collaboration among researchers in the UK, Norway and the United States investigated whether host-encoded prion protein (PrP^C) variation explains interspecies difference in prion disease susceptibility. It is know that disease susceptibility patterns in ruminants (e.g., cows, sheep, deer) are dependent on sequence variants of the prion gene; however, identifiable disease-associated PrP polymorphism has not been comprehensively investigated in carnivores (e.g., domestic cats, large cats, bears, mink, etc.) that are also known to be susceptible to prion disease.

Prion diseases cannot develop or replicate without host expression of PrP^C. In healthy animals, PrP^C is highly expressed in neural tissue, but also in many other cell-types. Infection develops when PrP^C is converted into abnormal PrP^Sc isoform that catalyzes other PrP^C -> PrP^Sc conversions whereby the abnormal protein then accumulates into amyloid fibrils in neural and lymphoid tissues. Protein isoform conversion and accumulation leads to neurological disease known as spongiform encephalopathy or prion disease. Most FSE cases occurred in parallel to the BSE epidemic, supporting exposure of affected cats to feed contaminated with PrP^BSE as causation of the disease in cats. Ingested PrP^BSE initiates the abnormal isoform conversion. Whether cats or other groups of carnivore species can contract other prion diseases (e.g., chronic wasting disease) by ingestion in a natural setting remains an open question.

The researchers sequenced and compared the open reading frame of the PRNP gene encoding PrP^C protein from 609 animal samples comprising 29 species from 22 genera of carnivores. Samples included 249 samples from cat species represented by eight lineages of cats; amongst these samples were 15 FSE cases. Analysis of samples from 118 domestic cats from Europe and North America and from 9 domestic cat FSE cases from the UK did not encode an identifiable disease-associated PrP polymorphism. In addition, FSE cases from 6 cheetahs located in France (five) and Germany (one) were genotyped and no amino acid polymorphism was detected. The researchers inferred that FSE risk in the feline species was not controlled by highly susceptible PrP variants. The lack of PrP variants associated with FSE-infected cats and cheetahs indicated that these animals were not at higher genetic risk than other individuals of their species for prion disease. Furthermore, little genetic variation suggests that cats could have an unrestricted susceptibility to TSEs. [GO]

See also:

• Mathiason CK, Nalls AV, Seelig DM, et al. Susceptibility of domestic cats to chronic wasting disease. J Virol 2013;87:1947-1956. (free, full text)
• Salvadori C, Lossi L, Arispici M, et al. Spongiform neurodegenerative disease in a Persian kitten. J Feline Med Surg 2007;9:242-245.