Differential Expression of Cellular Prion Protein (PrP) in Mouse Hepatitis Virus Induced Neuroinflammation

Overview

Journal J Neurovirol

Publisher Springer

Specialties Microbiology
Neurology

Date 2024 Jun 26

PMID 38922550

Authors

Satavisha Ghosh

Rishika Jana

Soumen Jana

Rahul Basu

Madhurima Chatterjee

Nishtha Ranawat

Jayasri Das Sarma

Affiliations

Soon will be listed here.

Abstract

The cellular prion protein (PrP) is an extracellular cell membrane protein. Due to its diversified roles, a definite role of PrP has been difficult to establish. During viral infection, PrP has been reported to play a pleiotropic role. Here, we have attempted to envision the function of PrP in the neurotropic m-CoV-MHV-RSA59-induced model of neuroinflammation in C57BL/6 mice. A significant upregulation of PrP at protein and mRNA levels was evident in infected mouse brains during the acute phase of neuroinflammation. Furthermore, investigation of the effect of MHV-RSA59 infection on PrP expression in specific neuronal, microglial, and astrocytoma cell lines, revealed a differential expression of prion protein during neuroinflammation. Additionally, siRNA-mediated downregulation of prnp transcripts reduced the expression of viral antigen and viral infectivity in these cell lines. Cumulatively, our results suggest that PrP expression significantly increases during acute MHV-RSA59 infection and that PrP also assists in viral infectivity and viral replication.

References

Abskharon R, Wang F, Wohlkonig A, Ruan J, Soror S, Giachin G . Structural evidence for the critical role of the prion protein hydrophobic region in forming an infectious prion. PLoS Pathog. 2019; 15(12):e1008139. PMC: 6922452. DOI: 10.1371/journal.ppat.1008139. View

Advani V, Ivanov P . Translational Control under Stress: Reshaping the Translatome. Bioessays. 2019; 41(5):e1900009. PMC: 6541386. DOI: 10.1002/bies.201900009. View

Alais S, Soto-Rifo R, Balter V, Gruffat H, Manet E, Schaeffer L . Functional mechanisms of the cellular prion protein (PrP(C)) associated anti-HIV-1 properties. Cell Mol Life Sci. 2011; 69(8):1331-52. PMC: 11114771. DOI: 10.1007/s00018-011-0879-z. View

Altmeppen H, Prox J, Krasemann S, Puig B, Kruszewski K, Dohler F . The sheddase ADAM10 is a potent modulator of prion disease. Elife. 2015; 4. PMC: 4346534. DOI: 10.7554/eLife.04260. View

Bakkebo M, Mouillet-Richard S, Espenes A, Goldmann W, Tatzelt J, Tranulis M . The Cellular Prion Protein: A Player in Immunological Quiescence. Front Immunol. 2015; 6:450. PMC: 4557099. DOI: 10.3389/fimmu.2015.00450. View

Bertuchi F, Bourgeon D, Landemberger M, Martins V, Cerchiaro G . PrPC displays an essential protective role from oxidative stress in an astrocyte cell line derived from PrPC knockout mice. Biochem Biophys Res Commun. 2012; 418(1):27-32. DOI: 10.1016/j.bbrc.2011.12.098. View

Borchelt D, Koliatsos V, Guarnieri M, Pardo C, Sisodia S, Price D . Rapid anterograde axonal transport of the cellular prion glycoprotein in the peripheral and central nervous systems. J Biol Chem. 1994; 269(20):14711-4. View

Bose A, Basu R, Maulik M, Das Sarma J . Loss of Cx43-Mediated Functional Gap Junction Communication in Meningeal Fibroblasts Following Mouse Hepatitis Virus Infection. Mol Neurobiol. 2018; 55(8):6558-6571. PMC: 7090783. DOI: 10.1007/s12035-017-0861-3. View

Bose A, Kasle G, Jana R, Maulik M, Thomas D, Mulchandani V . Regulatory role of endoplasmic reticulum resident chaperone protein ERp29 in anti-murine β-coronavirus host cell response. J Biol Chem. 2022; 299(2):102836. PMC: 9788854. DOI: 10.1016/j.jbc.2022.102836. View

10.

Brown D, Besinger A, Herms J, Kretzschmar H . Microglial expression of the prion protein. Neuroreport. 1998; 9(7):1425-9. DOI: 10.1097/00001756-199805110-00032. View

11.

Carulla P, Bribian A, Rangel A, Gavin R, Ferrer I, Caelles C . Neuroprotective role of PrPC against kainate-induced epileptic seizures and cell death depends on the modulation of JNK3 activation by GluR6/7-PSD-95 binding. Mol Biol Cell. 2011; 22(17):3041-54. PMC: 3164453. DOI: 10.1091/mbc.E11-04-0321. View

12.

Carulla P, Llorens F, Matamoros-Angles A, Aguilar-Calvo P, Espinosa J, Gavin R . Involvement of PrP(C) in kainate-induced excitotoxicity in several mouse strains. Sci Rep. 2015; 5:11971. PMC: 4648388. DOI: 10.1038/srep11971. View

13.

Caruso P, Burla R, Piersanti S, Cherubini G, Remoli C, Martina Y . Prion expression is activated by Adenovirus 5 infection and affects the adenoviral cycle in human cells. Virology. 2009; 385(2):343-50. DOI: 10.1016/j.virol.2008.12.005. View

14.

Castle A, Gill A . Physiological Functions of the Cellular Prion Protein. Front Mol Biosci. 2017; 4:19. PMC: 5382174. DOI: 10.3389/fmolb.2017.00019. View

15.

Collins S, McLean C, Masters C . Gerstmann-Sträussler-Scheinker syndrome,fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies. J Clin Neurosci. 2001; 8(5):387-97. DOI: 10.1054/jocn.2001.0919. View

16.

Das Sarma J . A mechanism of virus-induced demyelination. Interdiscip Perspect Infect Dis. 2010; 2010:109239. PMC: 2905936. DOI: 10.1155/2010/109239. View

17.

Das Sarma J, Iacono K, Gard L, Marek R, Kenyon L, Koval M . Demyelinating and nondemyelinating strains of mouse hepatitis virus differ in their neural cell tropism. J Virol. 2008; 82(11):5519-26. PMC: 2395180. DOI: 10.1128/JVI.01488-07. View

18.

Das Sarma J, Kenyon L, Hingley S, Shindler K . Mechanisms of primary axonal damage in a viral model of multiple sclerosis. J Neurosci. 2009; 29(33):10272-80. PMC: 2747667. DOI: 10.1523/JNEUROSCI.1975-09.2009. View

19.

Das Sarma J, Scheen E, Seo S, Koval M, Weiss S . Enhanced green fluorescent protein expression may be used to monitor murine coronavirus spread in vitro and in the mouse central nervous system. J Neurovirol. 2002; 8(5):381-91. PMC: 7095158. DOI: 10.1080/13550280260422686. View

20.

DeDiego M, Nieto-Torres J, Regla-Nava J, Jimenez-Guardeno J, Fernandez-Delgado R, Fett C . Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol. 2013; 88(2):913-24. PMC: 3911641. DOI: 10.1128/JVI.02576-13. View