The amyloidoses are a group of protein misfolding disorders characterized by the accumulation of amyloid fibrils formed from a variety of proteins that, under normal physiological conditions, are harmless and soluble. Currently, 25 amyloid diseases have been identified, such as the prion diseases, Alzheimer’s disease, type 2 diabetes, and various systematic amyloidoses. Although the various proteins that can polymerize into amyloid fibrils have unrelated sequences, they can all form fibrils with a similar ultrastructural appearance. Among them, prion diseases such as transmissible spongiform encephalopathy (TSE), including scrapie in sheep, bovine spongiform encephalopathy (BSE), and chronic wasting disease (CWD) of deer and elk, are highly infectious. In these diseases, prion (PrPSc), an abnormal form of the host cellular prion protein (PrPC), induces the conformational change of PrPC to the PrPSc and causes a detectable phenotype or disease in the affected individual. AA amyloidosis is characterized by the systemic deposition of extracellular fibrils composed of amyloid A protein, primarily in the spleen; liver; and, to a lesser extent, in other organs. In most species, AA amyloidosis occurs sporadically and is typically secondary to chronic inflammation, infection, or neoplasia. Intriguing recent data suggest that AA amyloidosis could be transmitted by a prion-like infectious process through a seeding-nucleation mechanism.
The cheetah (Acinonyx jubatus) is in danger of extinction and is included on The World Conservation Union list of vulnerable species. Although efforts have been made in wildlife sanctuary parks and zoos worldwide to prevent extinction, a steady increase in the size of the cheetah population is hampered by the high prevalence of certain diseases in captive cheetahs. In particular, systemic AA amyloidosis is regarded as an increasingly important cause of morbidity and mortality in captive cheetahs as prevalence increased from 20% in pre-1990 reported necropsies to an unusual 70% of necropsied cheetahs in 1995. Despite much effort, the pathogenesis for AA amyloidosis in cheetahs is still only partially understood. However, environmental epidemiological studies indicate that breeding conditions have a prominent effect on the incidence of AA amyloidosis. A high rearing density is always associated with early age of onset, and with the high incidence and severity of AA amyloidosis, findings similar to sheep scrapie and cervid CWD. Thus, sustained epidemics of sheep scrapie and cervid CWD appear to be principally due to horizontal (animal to animal) transmission, although the routes of natural transmission remain to be clarified. The propagation of AA amyloidosis among captive cheetah populations may also depend on a horizontal transmission pathway. Identification of the mode of transmission is a prerequisite for disease control. This study shows that the faeces from a cheetah with AA amyloidosis can act as a possible transmission agent to accelerate the onset of AA amyloidosis.
Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease PNAS USA May 12, 2008
AA amyloidosis is one of the principal causes of morbidity and mortality in captive cheetahs (Acinonyx jubatus), which are in danger of extinction, but little is known about the underlying mechanisms. Given the transmissible characteristics of AA amyloidosis, transmission between captive cheetahs may be a possible mechanism involved in the high incidence of AA amyloidosis. In this study of animals with AA amyloidosis, we found that cheetah feces contained AA amyloid fibrils that were different from those of the liver with regard to molecular weight and shape and had greater transmissibility. The infectious activity of fecal AA amyloid fibrils was reduced or abolished by the protein denaturants 6M guanidine HCl and formic acid or by AA immunodepletion. Thus, we propose that feces are a vehicle of transmission that may accelerate AA amyloidosis in captive cheetah populations. These results provide a pathogenesis for AA amyloidosis and suggest possible measures for rescuing cheetahs from extinction.
But wait –
It might seem like prions are always bad news, but if that were true, they would be an evolutionary disadvantage and would surely have been lost. So the truth must be more complicated, and in tomorrow’s post, we’ll see how.