New data about the presence of prions
The identification of prion-like domains in multiple viral strains points to new areas to explore
NEW YORK—Recent research out of the Human Microbiology Institute (HMI) and Tetz Laboratories could answer several questions—and open the door for answers to several more—about prions and the roles they play in human viruses and neurodegenerative diseases. Their discovery of prion-like domains in a variety of viruses was published in Science and could connect some dots with regards to how prions enable infection.
Prions (also known as PrP) are a type of protein capable of self-propagation thanks to a β-sheet-rich conformation, according to HMI, which leads to the misfolding of proteins. As is well known in diseases such as Alzheimer’s and Parkinson’s disease, when misfolded proteins accumulate, it can result in neurotoxicity. Protein misfolding also features in ataxias and amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease.
Prions have been known to be a neurological nuisance before—one of the most well-known prion diseases is bovine spongiform encephalopathy, or “mad cow” disease. These neurodegenerative disorders are hallmarked by “neuronal loss and a failure to induce inflammatory response,” according to the U.S. Centers for Disease Control and Prevention. Similar to Alzheimer’s disease, mad cow disease also features amyloid plaques in the brain. However, as noted on a supplementary page on the Department of Chemistry at the University of Wisconsin’s website, “Chemical and biochemical analysis [has] showed that there was no difference in composition or primary structure between the normal, cellular form of PrP [PrPC] and the disease form of PrP [PrPSc]. Further analysis showed that PrPC can change into PrPSc when two of the alpha helices change into beta sheets. This beta sheet can then induce a similar change in another molecule of PrPC and hydrogen bond to it. The PrPScs then polymerize and come out of solution, forming the plaques found in Alzheimer’s patients and mad cows.”
Beyond those known areas, however, the Science paper’s abstract notes that prions have also “recently been shown to represent an important functional component in many prokaryotic and eukaryotic organisms and bacteriophages, confirming the previously unexplored important regulatory and functional roles. However, an in-depth analysis of these domains in eukaryotic viruses has not been performed … Our findings indicate that viral prion-like proteins can be found in different viruses of insects, plants, mammals, and humans. The analysis performed here demonstrated common patterns in the distribution of prion-like domains across viral orders and families, and revealed probable functional associations with different steps of viral replication and interaction with host cells. These data allow the identification of the viral prion-like proteins as potential novel regulators of viral infections.”
As detailed in the paper, Drs. George and Victor Tetz—CEO and scientific advisor of Tetz Laboratories, respectively—discovered 2,679 proteins in human viruses that possess prion-like structures. Combined with the fact that previous research has demonstrated that viruses are implicated in the aforementioned diseases, HMI noted in a press release that this discovery “for the first time proposes that the misfolding of proteins is the previously unknown pathway for these prions to infect humans.”
“In particular, this explains the previously unknown mechanisms of viral pathogenicity,” Victor Tetz said in a press release. “We are very excited to advance our discoveries to develop principally novel classes of antiviral drugs linked to these viral proteins.”
The team scanned through 2,742,160 publicly available viral protein sequences looking for prionogenic domains (PrDs), and found that “PrD-containing proteins were found to be associated with the suppression of host complement activation and virus-induced changes in cells, including the modulation of host apoptotic process. We identified the PrDs in these proteins in many unrelated viruses of different hosts. The PrDs were primarily identified in human and insect viruses with demonstrated ability to establish persistent infections: Baculoviridae, HIV1, and Herpesviridae species, such as HSV1, Epstein-Barr virus, cytomegalovirus, and oncogenic HSV8. This indicates that the PrDs in these proteins may be implicated in the establishment of persistent viral infections and affect the adaptive immune response.”
These results, the authors noted, “may contribute to the better understanding of the host-viral interactions and the relationship between viral prions and pathogenicity.”