Prion expression is activated by Adenovirus 5 infection and affects the adenoviral cycle in human cells

Abstract

The prion protein is a cell surface glycoprotein whose physiological role remains elusive, while its implication in transmissible spongiform encephalopathies (TSEs) has been demonstrated. Multiple interactions between the prion protein and viruses have been described: viruses can act as co-factors in TSEs and life cycles of different viruses have been found to be controlled by prion modulation. We present data showing that human Adenovirus 5 induces prion expression. Inactivated Adenovirus did not alter prion transcription, while variants encoding for early products did, suggesting that the prion is stimulated by an early adenoviral function. Down-regulation of the prion through RNA interference showed that the prion controls adenovirus replication and expression. These data suggest that the prion protein could play a role in the defense strategy mounted by the host during viral infection, in a cell autonomous manner. These results have implications for the study of the prion protein and of associated TSEs.

Persistent retroviral infection with MoMuLV influences neuropathological signature and phenotype of prion disease

“…However, since these endogenous viruses did not have the capacity to give rise to replication competent virus particles, the role and impact of this up regulation is only descriptive until now and the impact of these findings has to be investigated in more detail. Conversely, PrP C expression is induced by certain viral infections [14]. PrP C binds to viral proteins and influences the expression or activation of murine and human retroviruses [40,48].…”

A Proautophagic Antiviral Role for the Cellular Prion Protein Identified by Infection with a Herpes Simplex Virus 1 ICP34.5 Mutant

“…These effects imply that autophagy induction has a cytoprotective role in pathogen clearance. Cellular PrP also restricts replication of several viruses, including adenovirus 5 in HuH7 cells (36), HIV-1 in 293T cells (37), and coxsackievirus B3 in cells derived from mouse brain (38). In addition, upregulation of cellular PrP in mouse spleen coincides with reduced replication of an endogenous murine retrovirus (39).…”

Aβ, tau, α-synuclein, huntingtin, TDP-43, PrP and AA are members of the innate immune system: a unifying hypothesis on the etiology of AD, PD, HD, ALS, CJD and RSA as innate immunity disorders

“…The ability of many amyloid proteins, including Aβ, α-synuclein, huntingtin, PrP, and AA, to assemble into membrane-damaging channels or pores has been documented in hundreds of studies (reviewed in 5-7). Also, there are direct experimental data and observations supporting the antimicrobial and antiviral activities of this group of putative innate immunity proteins (8)(9)(10)(11)(12)(13)(14)(15)(16)(17) and the interaction of these proteins with diverse infectious agents or with various arms of the immune system (e.g., see 18-33; note: though not recognized as such, the RNAi system is an important arm of the innate immune system; 5,34.) Although many of these studies were designed to address the pathogenic mechanisms by which these proteins cause disease, not their physiologic function, their results are nonetheless consistent with and support the new unifying hypothesis.…”