NEW YORK (GenomeWeb) – Gene expression patterns in cattle blood samples may help in identifying atypical forms of bovine spongiform encephalopathy before physical symptoms appear, according to a study published online this week in PLOS One.
Researchers from Italy and the US performed array-based transcriptomic profiling on whole blood samples from 10 cattle with or without atypical BSE — forms of the disease that are suspected of occurring spontaneously in some older cattle rather than through exposure to prion-infected feed.
The team uncovered nearly three-dozen genes that were differentially expressed in the BSE-infected cattle, both before and after the infection became obvious. Another 22-gene expression signature appeared to be specific to the pre-clinical stage, hinting that it may be possible to develop blood-based methods to detect the neurodegenerative disease and isolate affected animals before symptoms appear.
"Our findings suggest the intriguing possibility to take advantage of whole blood RNA transcriptional profiling for the pre-clinical identification of prion infection," senior author Giuseppe Legname, a functional and structural genomics researcher at the International School for Advanced Studies in Trieste, and his co-authors wrote.
Prion disease in cattle, commonly referred to as "mad cow disease," can take several different forms. Though classic BSE is one of the best known forms of transmissible spongiform encephalopathy in cattle, its prevalence has dropped dramatically in recent years due to growing awareness of the risks involved in exposing cattle to prions in feed, the team noted.
In its wake, there is growing concern over forms of BSE that involve prions with slightly different abnormally folded prion isoform properties. These atypical forms of the disease — together known as bovine amyloidotic spongiform encephalopathy, or BASE — include H-type BSE and L-type BSE, diseases that have been reported in cattle eight years old or older in North America, Europe, and Japan.
"[I]t has been postulated that, unlike classical BSE, cases of atypical BSE may have risen spontaneously, although transmission through feed or the environment cannot be ruled out," Legname and co-authors explained.
The researchers set out to search for potential diagnostic clues to the disease using blood samples from four cattle that had been inoculated with H-type BSE with, four cattle inoculated with L-type BSE, and two uninfected controls, all from the UK.
Using the Affymetrix GeneChip Bovine Genome Array, the team tested gene expression patterns in blood samples taken six months after inoculation but before clinical infection, and again around two years after infection during the clinical stage of BSE.
Compared to expression profiles in control cattle, the search initially identified 172 genes with specific expression patterns during clinical stages of atypical BSE infection, 78 genes with pre-clinical BSE-specific expression, and 32 genes that were differentially expressed in both pre-clinical and clinical blood samples.
The researchers saw shifts in the expression of specific immune genes during the transition from pre-clinical to clinical stages of disease, along with a marked decline in expression of SEL1L3. The gene's function is yet-to-be determined, they noted, though it codes for a transmembrane protein with a paralog involved in misfolded protein transport.
Intriguingly, their results also uncovered nine genes with enhanced expression and 13 genes with lower-than-usual levels in blood samples from infected, pre-clinical cattle relative to samples from both control cattle and cattle with full-blown BSE infection.
The team subsequently tested a subset of the differentially expressed genes from each stage of infection, verifying patterns for SEL1L3 and a handful of other genes. The authors cautioned that "the present results should be read as a first exploration of whole blood transcriptomics during a prion infection," but expressed optimism about eventually developing expression-based tools for early detection of atypical BSE.