What is it about?
These big RNA dataset studies show that when CJD infected neurons are induced to divide they rapidly lose their neuronal characteristics as well as their infectivity. However, when multiply passaged dividing cells are switched to a non-dividing or arrested state, using defined physiologic conditions, they progressively develop high levels of infection over several weeks. This shows that apparently uninfected neuronal precursor cells continue to carry latent infectious particles. In contrast to uninfected neurons treated in parallel, re-arrested infectious cells also showed imprinted effects of their previous infection 1) by expression of many RNA transcripts facilitating their escape from complete arrest, 2) their reduced neuronal differentiation markers including prion protein, and 3) their robust upregulation of a plethora of interferon pathways and innate immune responses that are commonly activated by viral infections.
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Why is it important?
The above studies show CJD agents can persist in a non-productive state that can be activated physiologically. This first cellular model of latent infection is most relevant for human iatrogenic cases of human growth hormone contaminated CJD transmission where the infectious agent can remain silent for 30 years or more before producing disease. For many years these infectious agents have been considered immunologically silent and host prion protein and its misfolded amyloid form does not elicit the innate immune responses shown above. Some of the above innate immune pathways can be used to uncover latent infections by modifying the physiologic environment of cells in culture.
Perspectives
Protein misfolding and amyloid can be a sign of late damage, and, like a scar, can be due to different causes such as toxins, infections, and trauma. Just looking at the scar doesn’t tell you their initiating cause. We think that hit and run, latent and unknown environmental and metagenomic elements deserve more study as initiating causes of neurodegeneration.
laura manuelidis
Yale University
Read the Original
This page is a summary of: Proliferative arrest induces neuronal differentiation and innate immune responses in normal and Creutzfeldt-Jakob Disease agent (CJ) infected rat septal neurons, PLOS One, May 2025, PLOS,
DOI: 10.1371/journal.pone.0323825.
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