Estrés celular y SARS-CoV-2.
DOI:
https://doi.org/10.54139/salus.v25i3.129Palabras clave:
SARS-CoV-2, COVID-19, estrés celular, UPR, estrés oxidativo, autofagiaResumen
Introducción: El agente etiológico responsable de COVID-19, SARSCoV-2, es un virus ARN perteneciente a la familia Coronaviridae. Durante la replicación, los componentes virales interactúan con la maquinaria celular induciendo alteraciones en la fisiología celular, lo que contribuye a la patogénesis del virus. Método: Revisión bibliográfica en NCBI/Pubmed sobre estrés celular y SARS-CoV-2 Hallazgos de interpretación: Como respuesta a la infección, en la célula hospedadora se activan vías de señalización, cuyo principal objetivo es recuperar la homeostasis y de no lograrlo, inducir a la activación de la muerte celular. Entre las vías de señalización mejor caracterizadas, destacan las rutas de estrés celular como el estrés oxidativo, la UPR (Respuesta a proteínas no plegadas), y la autofagia, las cuales son evolutivamente bien conservadas y además están interconectadas entre sí. Hay fuerte evidencia teórica y experimental de diversas interacciones de algunos componentes de estas rutas con distintas proteínas virales de los coronavirus, y ya se han adelantado algunos estudios con SARS-CoV-2. En esta revisión, resaltamos algunas de las rutas celulares-virus que se han caracterizado hasta el momento.
Reflexiones finales: Aún queda mucho por entender de estas rutas y su relación con las infecciones virales; esto pudiera constituir un importante blanco para la investigación y desarrollo de terapias antivirales.
Descargas
Citas
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 2020; 382:727-733. https://doi.org/10.1056/NEJMoa2001017
Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020; 28:9(1):221-236. https://doi.org/10.1080/22221751.2020.1719902
Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol 2020; 92(4): 418-423. https://doi.org/10.1002/jmv.25681
Perlman S, Netland J. Coronaviruses post-SARS: Update on replication and pathogenesis. Nat Rev Microbiol 2009; 7(6):439-450. https://doi.org/10.1038/nrmicro2147
Gaut JR, Hendershot LM. The modification and assembly of proteins in the endoplasmic reticulum. Curr Opin Cell Biol. 1993; 5(4):589-595. https://doi.org/10.1016/0955-0674(93)90127-C
Hetz C, Martinon F, Rodriguez D, Glimcher LH. The unfolded protein response: integrating stress signals through the stress sensor IRE1α. Physiol Rev. 2011;91(4):1219-1243. https://doi.org/10.1152/physrev.00001.2011
Minakshi R, Padhan K, Rani M, Khan N, Ahmad F, Jameel S. The SARS Coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor. PLoS One. 2009; 17; 4(12):e8342. https://doi.org/10.1371/journal.pone.0008342.
Chan SW. The unfolded protein response in virus infections. Front Microbiol 2014; 30; 5:518. https://doi.org/10.3389/fmicb.2014.00518.
Malhotra JD, Kaufman RJ. Endoplasmic reticulum stress and oxidative stress: A vicious cycle or a double-edged sword? Antioxid Redox Signal 2007; 9(12):2277-2293. https://doi.org/10.1089/ars.2007.1782.
Walter P, Ron D. The unfolded protein response: From stress pathway to homeostatic regulation. Science 2011; 334(6059):1081-1086. https://doi.org/10.1126/science.1209038.
Ghavami S, Sharma P, Yeganeh B, Ojo OO, Jha A, Mutawe MM, et al. Airway mesenchymal cell death by mevalonate cascade inhibition: integration of autophagy, unfolded protein response and apoptosis focusing on Bcl2 family proteins. Biochim Biophys Acta. 2014;1843(7):1259-1271. https://doi.org/10.1016/j.bbamcr.2014.03.006.
Ghavami S, Yeganeh B, Zeki AA, Shojaei S, Kenyon NJ, Ott S, et al. Autophagy and the unfolded protein response promote profibrotic effects of TGF-β1 in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2018 1; 314(3):L493-L504. https://doi.org/10.1152/ajplung.00372.2017.
Cottam EM, Maier HJ, Manifava M, Vaux LC, Chandra- Schoenfelder P, Gerner W, et al. Coronavirus nsp6 proteins generate autophagosomes from the endoplasmic reticulum via an omegasome intermediate. Autophagy 2011; 7(11): 1335-1347. https://doi.org/10.4161/auto.7.11.16642.
Zhao Z, Lu K, Mao B, Liu S, Trilling M, Huang A, et al. The interplay between emerging human coronavirus infections and autophagy. Emerg Microbes Infect 2021; 10(1):196-205 https://doi.org/10.1080/22221751.2021.1872353.
Zhong J, Guo D, Chen CB, Wang W, Schuster M, Loibner H, Penninger JM, Scholey JW, Kassiri Z, Oudit GY. Prevention of angiotensin II-mediated renal oxidative stress, inflammation, and fibrosis by angiotensin-converting enzyme 2. Hypertension. 2011;57(2):314-322. https://doi.org/10.1161/HYPERTENSIONAHA.110.164244.
Kim SM, Kim YG, Jeong KH, Lee SH, Lee TW, Ihm CG, Moon JY. Angiotensin II-induced mitochondrial Nox4 is a major endogenous source of oxidative stress in kidney tubular cells. PLoS One. 2012; 7(7):e39739. doi:https://doi.org/10.1371/journal.pone.0039739.
Suhail S, Zajac J, Fossum C, Lowater H, McCracken C, Severson N, et al. Role of oxidative stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) infection: a review. Protein J 2020; 39(6): 644-656. https://doi.org/10.1007/s10930-020-09935-8.
V'kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2 Nat Rev Microbiol 2021;19, 155-170 https://doi.org/10.1038/s41579-020-00468-6.
Wang MY, Zhao R, Gao LJ, Gao XF, Wang DP, Cao JM. SARS-CoV-2: structure, biology, and structure-based therapeutics development. Front Cell Infect Microbiol. 2020; 10:587269. https://doi.org/10.3389/fcimb.2020.587269
Glebov OO. Understanding SARS-CoV-2 endocytosis for COVID-19 drug repurposing. FEBS J 2020; 287(17): 3664-3671. https://doi.org/10.1111/febs.15369
Santerre, M., Arjona, S.P., Allen, C.N. et al. Why do SARS-CoV-2 NSPs rush to the ER?. J Neurol 2021;268: 2013-2022. https://doi.org/10.1007/s00415-020-10197-8
Fung TS, Liu DX. Human Coronavirus: host-pathogen interaction. Annu Rev Microbiol 2019; 73:529-557. https://doi.org/10.1146/annurev-micro-020518-115759.
Sies H. Oxidative stress: from basic research to clinical application. Am J Med. 1991; 91(3C): 31S-38S. https://doi.org/10.1016/0002-9343(91)90281-2.
Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018; 13:757-772. https://doi.org/10.2147/CIA.S158513.
Zhang Z, Rong L, Li YP. Flaviviridae Viruses and oxidative stress: implications for viral pathogenesis. Oxid Med Cell Longev. 2019; 2019:1409582. https://doi.org/10.1155/2019/1409582.
Roy J, Galano JM, Durand T, Le Guennec JY, Lee JC. Physiological role of reactive oxygen species as promoters of natural defenses. FASEB J 2017; 31(9):3729-3745. https://doi.org/10.1096/fj.201700170R.
Reshi ML, Su YC, Hong JR. RNA Viruses: ROS-mediated cell death. Int J Cell Biol. 2014; 2014:467452. https://doi.org/ 10.1155/2014/467452. https://doi.org/10.1155/2014/467452.
Checconi P, De Angelis M, Marcocci ME, Fraternale A, Magnani M, Palamara AT, Nencioni L. Redox-Modulating agents in the treatment of viral infections. Int J Mol Sci. 2020; 21(11):4084. https://doi.org/10.3390/ijms21114084.
Beck MA, Handy J, Levander OA. The role of oxidative stress in viral infections. Ann N Y Acad Sci. 2000; 917:906-912. https://doi.org/10.1111/j.1749-6632.2000.tb05456.x.
Lin CW, Lin KH, Hsieh TH, Shiu SY, Li JY. Severe acute respiratory syndrome coronavirus 3C-like protease-induced apoptosis. FEMS Immunol Med Microbiol. 2006; 46(3): 375-380. https://doi.org/10.1111/j.1574-695X.2006.00045.x.
Kanzawa N, Nishigaki K, Hayashi T, Ishii Y, Furukawa S, Niiro A, et al. Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF-kappaB activation. FEBS Lett. 2006; 580(30): 6807-6812. https://doi.org/10.1016/j.febslet.2006.11.046.
Chan CM, Tsoi H, Chan WM, Zhai S, Wong CO, Yao X, Chan WY, Tsui SK, Chan HY. The ion channel activity of the SARS-coronavirus 3a protein is linked to its pro-apoptotic function. Int J Biochem Cell Biol. 2009; 41(11): 2232-2239. https://doi.org/10.1016/j.biocel.2009.04.019.
Delgado-Roche L, Mesta F. Oxidative stress as key player in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) infection. Arch Med Res 2020; 51(5):384-387. https://doi.org/10.1016/j.arcmed.2020.04.019.
Issa E, Merhi G, Panossian B, Salloum T, Tokajian S. SARS-CoV-2 and ORF3a: nonsynonymous mutations, functional domains, and viral pathogenesis. mSystems. 2020; 5(3):e00266- 20. https://doi.org/10.1128/mSystems.00266-20.
Lingappan K. NF-κB in oxidative stress. Curr Opin Toxicol 2018; 7:81-86. https://doi.org/10.1016/j.cotox.2017.11.002.
Zhang L, Wei L, Jiang D, Wang J, Cong X, Fei R. SARS-CoV nucleocapsid protein induced apoptosis of COS-1 mediated by the mitochondrial pathway. Artif Cells Blood Substit Immobil Biotechnol. 2007; 35(2): 237-253. https://doi.org/10.1080/10731190601188422.
Padhan K, Minakshi R, Towheed MAB, Jameel S. Severe acute respiratory syndrome coronavirus 3a protein activates the mitochondrial death pathway through p38 MAP kinase activation. J Gen Virol. 2008; 89(Pt 8):1960-1969. https://doi.org/10.1099/vir.0.83665-0.
Battagello DS, Dragunas G, Klein MO, Ayub ALP, Velloso FJ, Correa RG. Unpuzzling COVID-19: tissue-related signaling pathways associated with SARS-CoV-2 infection and transmission. Clin Sci (Lond). 2020; 134(16): 2137-2160. https://doi.org/10.1042/CS20200904.
Bartoszewski R, Dabrowski M, Jakiela B, Matalon S, Harrod KS, Sanak M, et al. SARS-CoV-2 may regulate cellular responses through depletion of specific host miRNAs. Am J Physiol Lung Cell Mol Physiol 2020; 319(3): L444-L455. https://doi.org/10.1152/ajplung.00252.2020.
Paladino L, Vitale AM, Caruso Bavisotto C, Conway de Macario E, Cappello F, Macario AJL, Gammazza AM. The role of molecular chaperones in virus infection and implications for understanding and treating COVID-19. J Clin Med. 2020; 9(11): 3518. https://doi.org/10.3390/jcm9113518.
Fukushi M, Yoshinaka Y, Matsuoka Y, Hatakeyama S, Ishizaka Y, Kirikae T, Sasazuki T, Miyoshi-Akiyama T. Monitoring of S protein maturation in the endoplasmic reticulum by calnexin is important for the infectivity of severe acute respiratory syndrome coronavirus. J Virol. 2012; 86(21):11745-11753 https://doi.org/10.1128/JVI.01250-12.
Fung TS, Liu DX. Coronavirus infection, ER stress, apoptosis and innate immunity. Front Microbiol. 2014; 5:296. https://doi.org/10.3389/fmicb.2014.00296.
Khomari F, Nabi-Afjadi M, Yarahmadi S. Eskandari H, Bahreini E. Effects of cell proteostasis network on the survival of SARS-CoV-2. Biol Proced Online 2021; 23(1):8 https://doi.org/10.1186/s12575-021-00145-9.
Ibrahim IM, Abdelmalek DH, Elfiky AA. GRP78: A cell's response to stress. Life Sci. 2019; 226:156-163. https://doi.org/10.1016/j.lfs.2019.04.022
Yeung YS, Yip CW, Hon CC, Chow KY, Ma IC, Zeng F, Leung FC. Transcriptional profiling of Vero E6 cells over-expressing SARS-CoV S2 subunit: insights on viral regulation of apoptosis and proliferation. Virology. 2008; 71(1): 32-43. https://doi.org/10.1016/j.virol.2007.09.016
Fung TS, Huang M, Liu DX. Coronavirus-induced ER stress response and its involvement in regulation of coronavirus-host interactions. Virus Res 2014; 194:110-123. https://doi.org/10.1016/j.virusres.2014.09.016.
Krähling V, Stein DA, Spiegel M, Weber F, Mühlberger E. Severe acute respiratory syndrome coronavirus triggers apoptosis via protein kinase R but is resistant to its antiviral activity. J Virol 2009; 83(5):2298-2309. https://doi.org/10.1128/JVI.01245-08
DeDiego ML, Nieto-Torres JL, Jiménez-Guardeño JM, Regla-Nava JA, Alvarez E, Oliveros JC, Zhao J, Fett C, Perlman S, Enjuanes L. Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress response and apoptosis. PLoS Pathog. 2011;7(10):e1002315. https://doi.org/10.1371/journal.ppat.1002315.
Sung SC, Chao CY, Jeng KS, Yang JY, Lai MM. The 8ab protein of SARS-CoV is a luminal ER membrane-associated protein and induces the activation of ATF6. Virology 2009; 387(2):402-413. https://doi.org/10.1016/j.virol.2009.02.021
Rashid F, Dzakah EE, Wang H, Tang S. The ORF8 protein of SARS-CoV-2 induced endoplasmic reticulum stress and mediated immune evasion by antagonizing production of interferon beta. Virus Res. 2021; 296:198350 https://doi.org/10.1016/j.virusres.2021.198350
Gotoh T, Oyadomari S, Mori K, Mori M. Nitric oxide-induced apoptosis in RAW 264.7 macrophages is mediated by endoplasmic reticulum stress pathway involving ATF6 and CHOP. J Biol Chem 2002; 277(14):12343-12350. https://doi.org/10.1074/jbc.M107988200
Morishima N, Nakanishi K, Nakano A. Activating transcription factor-6 (ATF6) mediates apoptosis with reduction of myeloid cell leukemia sequence 1 (Mcl-1) protein via induction of WW domain binding protein 1. J Biol Chem. 2011; 286(40): 35227-35235. https://doi.org/10.1074/jbc.M111.233502
Uhal BD, Li X, Piasecki CC, Molina-Molina M. Angiotensin signalling in pulmonary fibrosis. International J Biochem Cell Biol 2012;44(3):465-468 https://doi.org/10.1016/j.biocel.2011.11.019
Cao X, Lu XM, Tuo X, Liu JY, Zhang YC, Song LN, Cheng ZQ, Yang JK, Xin Z. Angiotensin-converting enzyme 2 regulates endoplasmic reticulum stress and mitochondrial function to preserve skeletal muscle lipid metabolism. Lipids Health Dis 2019; 18(1):207. https://doi.org/10.1186/s12944-019-1145-x.
Aman Y, Schmauck-Medina T, Hansen M, Morimoto RI, Simon AK, Bjedov I, et al. Autophagy in healthy aging and disease. Nat Aging 2021;1(8): 634-650. https://doi.org/10.1038/s43587-021-00098-4
Shojaei S, Suresh M, Klionsky DJ, Labouta HI, Ghavami S. Autophagy and SARS-CoV-2 infection: a possible smart targeting of the autophagy pathway. Virulence 2020;11(1):805-810. https://doi.org/10.1080/21505594.2020.1780088
Hayn M, Hirschenberger M, Koepke L, Nchioua R, Straub JH, Klute S et al. Systematic functional analysis of SARSCoV-2 proteins uncovers viral innate immune antagonists and remaining vulnerabilities. Cell Rep 2021; 35(7):109126. https://doi.org/10.1016/j.celrep.2021.109126.
Descargas
Publicado
Cómo citar
Número
Sección
Licencia
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-SinDerivadas 4.0.
