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Human coronavirus-induced neuronal programmed cell death is cyclophilin d dependent and potentially caspase dispensable.
J Virol. 2012 Jan; 86(1):81-93.JV

Abstract

Human coronaviruses (HCoV) are recognized respiratory pathogens. Some HCoV strains, including HCoV-OC43, can invade the central nervous system, where they infect neurons, with unclear consequences. We have previously reported that HCoV-OC43 infection of human neurons activates the unfolded-protein response and caspase-3 and induces cell death and that the viral spike (S) glycoprotein is involved in the process. We now report on underlying mechanisms associated with the induction of programmed cell death (PCD) after infection by the reference HCoV-OC43 virus (rOC/ATCC) and a more neurovirulent and cytotoxic HCoV-OC43 variant harboring two point mutations in the S glycoprotein (rOC/U(S183-241)). Even though caspase-3 and caspase-9 were both activated after infection, the use of caspase inhibitors neither reduced nor delayed virus-induced PCD, suggesting that these proteases are not essential in the process. On the other hand, the proapoptotic proteins BAX, cytochrome c (CytC), and apoptosis-inducing factor (AIF) were relocalized toward the mitochondria, cytosol, and nucleus, respectively, after infection by both virus variants. Moreover, LA-N-5 neuronal cells treated with cyclosporine (CsA), an inhibitor of the mitochondrial permeabilization transition pore (mPTP), or knocked down for cyclophilin D (CypD) were completely protected from rOC/ATCC-induced neuronal PCD, underlining the involvement of CypD in the process. On the other hand, CsA and CypD knockdown had moderate effects on rOC/U(S183-241)-induced PCD. In conclusion, our results are consistent with mitochondrial AIF and cyclophilin D being central in HCoV-OC43-induced PCD, while caspases appear not to be essential.

Authors+Show Affiliations

Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, Laval, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22013052

Citation

Favreau, Dominique J., et al. "Human Coronavirus-induced Neuronal Programmed Cell Death Is Cyclophilin D Dependent and Potentially Caspase Dispensable." Journal of Virology, vol. 86, no. 1, 2012, pp. 81-93.
Favreau DJ, Meessen-Pinard M, Desforges M, et al. Human coronavirus-induced neuronal programmed cell death is cyclophilin d dependent and potentially caspase dispensable. J Virol. 2012;86(1):81-93.
Favreau, D. J., Meessen-Pinard, M., Desforges, M., & Talbot, P. J. (2012). Human coronavirus-induced neuronal programmed cell death is cyclophilin d dependent and potentially caspase dispensable. Journal of Virology, 86(1), 81-93. https://doi.org/10.1128/JVI.06062-11
Favreau DJ, et al. Human Coronavirus-induced Neuronal Programmed Cell Death Is Cyclophilin D Dependent and Potentially Caspase Dispensable. J Virol. 2012;86(1):81-93. PubMed PMID: 22013052.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human coronavirus-induced neuronal programmed cell death is cyclophilin d dependent and potentially caspase dispensable. AU - Favreau,Dominique J, AU - Meessen-Pinard,Mathieu, AU - Desforges,Marc, AU - Talbot,Pierre J, Y1 - 2011/10/19/ PY - 2011/10/21/entrez PY - 2011/10/21/pubmed PY - 2012/2/15/medline SP - 81 EP - 93 JF - Journal of virology JO - J Virol VL - 86 IS - 1 N2 - Human coronaviruses (HCoV) are recognized respiratory pathogens. Some HCoV strains, including HCoV-OC43, can invade the central nervous system, where they infect neurons, with unclear consequences. We have previously reported that HCoV-OC43 infection of human neurons activates the unfolded-protein response and caspase-3 and induces cell death and that the viral spike (S) glycoprotein is involved in the process. We now report on underlying mechanisms associated with the induction of programmed cell death (PCD) after infection by the reference HCoV-OC43 virus (rOC/ATCC) and a more neurovirulent and cytotoxic HCoV-OC43 variant harboring two point mutations in the S glycoprotein (rOC/U(S183-241)). Even though caspase-3 and caspase-9 were both activated after infection, the use of caspase inhibitors neither reduced nor delayed virus-induced PCD, suggesting that these proteases are not essential in the process. On the other hand, the proapoptotic proteins BAX, cytochrome c (CytC), and apoptosis-inducing factor (AIF) were relocalized toward the mitochondria, cytosol, and nucleus, respectively, after infection by both virus variants. Moreover, LA-N-5 neuronal cells treated with cyclosporine (CsA), an inhibitor of the mitochondrial permeabilization transition pore (mPTP), or knocked down for cyclophilin D (CypD) were completely protected from rOC/ATCC-induced neuronal PCD, underlining the involvement of CypD in the process. On the other hand, CsA and CypD knockdown had moderate effects on rOC/U(S183-241)-induced PCD. In conclusion, our results are consistent with mitochondrial AIF and cyclophilin D being central in HCoV-OC43-induced PCD, while caspases appear not to be essential. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/22013052/Human_coronavirus_induced_neuronal_programmed_cell_death_is_cyclophilin_d_dependent_and_potentially_caspase_dispensable_ L2 - https://journals.asm.org/doi/10.1128/JVI.06062-11?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -