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Coronaviruses

Editor-in-Chief

ISSN (Print): 2666-7967
ISSN (Online): 2666-7975

Mini-Review Article

Mechanistic Insights on Viral Factors Involved in Asymptomatic COVID-19 Pathogenesis

Author(s): Satinder Kaur, Renu Bala, Prakash Chandra Mishra, Vineeta Singh* and Rachna Hora*

Volume 4, Issue 3, 2023

Published on: 18 September, 2023

Article ID: e130923220999 Pages: 12

DOI: 10.2174/2666796704666230913105109

Price: $65

Abstract

SARS-CoV-2 infection may cause asymptomatic, pre-symptomatic or symptomatic COVID-19 disease. While symptomatic infections are at the centre stage for disease diagnosis and treatment, asymptomatic and pre-symptomatic cases heighten the challenge of transmission tracking ultimately leading to failure of control interventions. Asymptomatic cases appear due to a variety of host and viral factors and contribute substantially to the total number of infections. Through this article, we have tried to assemble existing information about the role of viral factors and mechanisms involved in the development of asymptomatic COVID-19. The significance of ‘PLpro’- a protease of Nidovirales order that removes ubiquitin and ISG15 from host proteins to regulate immune responses against the virus and hence disease presentation has been highlighted. PL-pro dampens inflammatory and antiviral responses, leading to asymptomatic infection. 11083G>T-(L37F) mutation in ‘Nsp6’ of SARS-CoV-2 also diminishes the innate immune response leading to asymptomatic infections. It is, therefore, pertinent to understand the role of proteins like PLpro and Nsp6 in SARS-CoV-2 biology for the development of transmission control measures against COVID-19. This review focuses on viral molecular mechanisms that alter disease severity and highlights compounds that work against such regulatory SARS-CoV-2 proteins.

Graphical Abstract

[1]
To KKW, Sridhar S, Chiu KHY, et al. Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic. Emerg Microbes Infect 2021; 10(1): 507-35.
[http://dx.doi.org/10.1080/22221751.2021.1898291] [PMID: 33666147]
[2]
Bajgain KT, Badal S, Bajgain BB, Santana MJ. Prevalence of comorbidities among individuals with COVID-19: A rapid review of current literature. Am J Infect Control 2021; 49(2): 238-46.
[http://dx.doi.org/10.1016/j.ajic.2020.06.213] [PMID: 32659414]
[3]
Gorbalenya AE, Baker SC, Baric RS, et al. The species Severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 2020; 5(4): 536-44.
[http://dx.doi.org/10.1038/s41564-020-0695-z] [PMID: 32123347]
[4]
WHO Coronavirus (COVID-19) Dashboard. 2019. Avaialble From:https://covid19.who.int
[5]
Huang L, Han R, Ai T, et al. Serial Quantitative Chest CT Assessment of COVID-19: A Deep Learning Approach. Radiol Cardiothorac Imaging 2020; 2(2): e200075.
[http://dx.doi.org/10.1148/ryct.2020200075] [PMID: 33778562]
[6]
Coronavirus disease 2019 (COVID-19): Situation report, 73. 2020. Avaialble From: https://apps.who.int/iris/handle/10665/331686
[7]
Gao Z, Xu Y, Sun C, et al. A systematic review of asymptomatic infections with COVID-19. J Microbiol Immunol Infect 2021; 54(1): 12-6.
[http://dx.doi.org/10.1016/j.jmii.2020.05.001] [PMID: 32425996]
[8]
Avanzato VA, Matson MJ, Seifert SN, et al. Case Study: Prolonged Infectious SARS-CoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer. Cell 2020; 183(7): 1901-1912.e9.
[http://dx.doi.org/10.1016/j.cell.2020.10.049] [PMID: 33248470]
[9]
Healthcare Workers: Information on COVID-19. 2020. Available From: https://www.cdc.gov/coronavirus/2019-ncov/hcp/index.html
[10]
Furukawa N W, Brooks J T, Sobel J. Evidence Supporting Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 While Presymptomatic or Asymptomatic. Emerg Infect Dis 2020; 26(7): e201595.
[http://dx.doi.org/10.3201/eid2607.201595]
[11]
28% of 40,184 Covid-19 cases in India till April 30 asymptomatic: Study. 2022. Available From:https://www.indiatoday.in/india/story/28-percent-of-40184-covid19-cases-india-till-april-30-asymptomatic-study-1683756-2020-05-30
[12]
Day M. Covid-19: Four fifths of cases are asymptomatic, China figures indicate. BMJ 2020; 369.
[13]
Day M. Covid-19: Identifying and isolating asymptomatic people helped eliminate virus in Italian village BMJ 2020; 368: m1165.
[14]
Kim G, Kim MJ, Ra SH, et al. Clinical characteristics of asymptomatic and symptomatic patients with mild COVID-19. Clin Microbiol Infect 2020; 26(7): 948.e1-3.
[http://dx.doi.org/10.1016/j.cmi.2020.04.040] [PMID: 32360780]
[15]
Mizumoto K, Kagaya K, Zarebski A, Chowell G. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill 2020; 25(10): 2000180.
[http://dx.doi.org/10.2807/1560-7917.ES.2020.25.10.2000180] [PMID: 32183930]
[16]
Johansson MA, Quandelacy TM, Kada S. SARS-CoV-2 Transmission From People Without COVID-19 Symptoms. JAMA Netw Open 2021; 4(1): e2035057.
[17]
Mehta NS, Mytton OT, Mullins EWS, et al. SARS-CoV-2 (COVID-19): What Do We Know About Children? A Systematic Review. Clin Infect Dis 2020; 71(9): 2469-79.
[http://dx.doi.org/10.1093/cid/ciaa556] [PMID: 32392337]
[18]
Hasanoglu I, Korukluoglu G, Asilturk D, et al. Higher viral loads in asymptomatic COVID-19 patients might be the invisible part of the iceberg. Infection 2021; 49(1): 117-26.
[http://dx.doi.org/10.1007/s15010-020-01548-8] [PMID: 33231841]
[19]
Weir EK, Thenappan T, Bhargava M, Chen Y. Does vitamin D deficiency increase the severity of COVID-19? Clin Med (Lond) 2020; 20(4): e107-8.
[http://dx.doi.org/10.7861/clinmed.2020-0301] [PMID: 32503801]
[20]
Secolin R, de Araujo TK, Gonsales MC, et al. Genetic variability in COVID-19-related genes in the Brazilian population. Hum Genome Var 2021; 8(1): 15.
[http://dx.doi.org/10.1038/s41439-021-00146-w] [PMID: 33824725]
[21]
Sefik E, Qu R, Junqueira C, et al. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 2022; 606(7914): 585-93.
[http://dx.doi.org/10.1038/s41586-022-04802-1] [PMID: 35483404]
[22]
Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: Immunity, inflammation and intervention. Nat Rev Immunol 2020; 20(6): 363-74.
[http://dx.doi.org/10.1038/s41577-020-0311-8] [PMID: 32346093]
[23]
Veras FP, Pontelli MC, Silva CM, et al. SARS-CoV-2–triggered neutrophil extracellular traps mediate COVID-19 pathology. J Exp Med 2020; 217(12): e20201129.
[http://dx.doi.org/10.1084/jem.20201129] [PMID: 32926098]
[24]
Jayarangaiah A, Kariyanna PT, Chen X, Jayarangaiah A, Kumar A. COVID-19-Associated Coagulopathy: An Exacerbated Immunothrombosis Response. Clin Appl Thromb Hemost 2020; 26.
[http://dx.doi.org/10.1177/1076029620943293] [PMID: 32735131]
[25]
Schneider WM, Chevillotte MD, Rice CM. Interferon-stimulated genes: A complex web of host defenses. Annu Rev Immunol 2014; 32(1): 513-45.
[http://dx.doi.org/10.1146/annurev-immunol-032713-120231] [PMID: 24555472]
[26]
Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol 2014; 14(1): 36-49.
[http://dx.doi.org/10.1038/nri3581] [PMID: 24362405]
[27]
Isaacson MK, Ploegh HL. Ubiquitination, ubiquitin-like modifiers, and deubiquitination in viral infection. Cell Host Microbe 2009; 5(6): 559-70.
[http://dx.doi.org/10.1016/j.chom.2009.05.012] [PMID: 19527883]
[28]
Smith S, Jefferies C. Role of DNA/RNA sensors and contribution to autoimmunity. Cytokine Growth Factor Rev 2014; 25(6): 745-57.
[http://dx.doi.org/10.1016/j.cytogfr.2014.07.019] [PMID: 25193293]
[29]
Liu S, Cai X, Wu J, et al. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science 2015; 347(6227): aaa2630.
[http://dx.doi.org/10.1126/science.aaa2630] [PMID: 25636800]
[30]
Hu H, Sun SC. Ubiquitin signaling in immune responses. Cell Res 2016; 26(4): 457-83.
[http://dx.doi.org/10.1038/cr.2016.40] [PMID: 27012466]
[31]
Dikic I, Wakatsuki S, Walters KJ. Ubiquitin-binding domains — from structures to functions. Nat Rev Mol Cell Biol 2009; 10(10): 659-71.
[http://dx.doi.org/10.1038/nrm2767] [PMID: 19773779]
[32]
Pickart CM, Eddins MJ. Ubiquitin: Structures, functions, mechanisms. Biochim Biophys Acta Mol Cell Res 2004; 1695(1-3): 55-72.
[http://dx.doi.org/10.1016/j.bbamcr.2004.09.019] [PMID: 15571809]
[33]
Chernorudskiy AL, Gainullin MR. Ubiquitin system: Direct effects join the signaling. Sci Signal 2013; 6(280): pe22-.
[http://dx.doi.org/10.1126/scisignal.2004251] [PMID: 23779085]
[34]
Gainullin MR. The Ubiquitination Machinery of the Ubiquitin System Arabidopsis Book 2014; 12: e0174.
[35]
McDowell GS, Philpott A. Non-canonical ubiquitylation: Mechanisms and consequences. Int J Biochem Cell Biol 2013; 45(8): 1833-42.
[http://dx.doi.org/10.1016/j.biocel.2013.05.026] [PMID: 23732108]
[36]
Davis ME, Gack MU. Ubiquitination in the antiviral immune response. Virology 2015; 479-480: 52-65.
[http://dx.doi.org/10.1016/j.virol.2015.02.033] [PMID: 25753787]
[37]
Kawadler H, Yang X. Lys63-linked polyubiquitin chains: Linking more than just ubiquitin. Cancer Biol Ther 2006; 5(10): 1273-4.
[http://dx.doi.org/10.4161/cbt.5.10.3289] [PMID: 16969079]
[38]
Reyes-Turcu FE, Ventii KH, Wilkinson KD. Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annu Rev Biochem 2009; 78(1): 363-97.
[http://dx.doi.org/10.1146/annurev.biochem.78.082307.091526] [PMID: 19489724]
[39]
Loeb KR, Haas AL. The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular proteins. J Biol Chem 1992; 267(11): 7806-13.
[http://dx.doi.org/10.1016/S0021-9258(18)42585-9] [PMID: 1373138]
[40]
Morales DJ, Lenschow DJ. The antiviral activities of ISG15. J Mol Biol 2013; 425(24): 4995-5008.
[http://dx.doi.org/10.1016/j.jmb.2013.09.041] [PMID: 24095857]
[41]
Hermann M, Bogunovic D. ISG15: In Sickness and in Health. Trends Immunol 2017; 38(2): 79-93.
[http://dx.doi.org/10.1016/j.it.2016.11.001] [PMID: 27887993]
[42]
Hermann M, Bogunovic D. ISG15 Arg151 and the ISG15- Conjugating Enzyme UbE1L Are Important for Innate Immune Control of Sindbis Virus. ASM J 2017; 83(4)
[43]
Lenschow DJ, Lai C, Frias-Staheli N, et al. IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis viruses. Proc Natl Acad Sci USA 2007; 104(4): 1371-6.
[http://dx.doi.org/10.1073/pnas.0607038104] [PMID: 17227866]
[44]
Rahnefeld A, Klingel K, Schuermann A, et al. Ubiquitin-like protein ISG15 (interferon-stimulated gene of 15 kDa) in host defense against heart failure in a mouse model of virus-induced cardiomyopathy. Circulation 2014; 130(18): 1589-600.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.009847] [PMID: 25165091]
[45]
Perng YC, Lenschow DJ. ISG15 in antiviral immunity and beyond. Nat Rev Microbiol 2018; 16(7): 423-39.
[http://dx.doi.org/10.1038/s41579-018-0020-5] [PMID: 29769653]
[46]
Malakhov MP, Malakhova OA, Kim KI, Ritchie KJ, Zhang DE. UBP43 (USP18) specifically removes ISG15 from conjugated proteins. J Biol Chem 2002; 277(12): 9976-81.
[http://dx.doi.org/10.1074/jbc.M109078200] [PMID: 11788588]
[47]
Pitha-Rowe I, Hassel BA, Dmitrovsky E. Involvement of UBE1L in ISG15 conjugation during retinoid-induced differentiation of acute promyelocytic leukemia. J Biol Chem 2004; 279(18): 18178-87.
[http://dx.doi.org/10.1074/jbc.M309259200] [PMID: 14976209]
[48]
Liu M, Hummer BT, Li X, Hassel BA. Camptothecin induces the ubiquitin-like protein, ISG15, and enhances ISG15 conjugation in response to interferon. J Interferon Cytokine Res 2004; 24(11): 647-54.
[http://dx.doi.org/10.1089/jir.2004.24.647] [PMID: 15684817]
[49]
Dao CT, Zhang D-E. ISG15: A ubiquitin-like enigma. Front Biosci 2005; 10(1-3): 2701-22.
[http://dx.doi.org/10.2741/1730] [PMID: 15970528]
[50]
Potter JL, Narasimhan J, Mende-Mueller L, Haas AL. Precursor processing of pro-ISG15/UCRP, an interferon-β-induced ubiquitin-like protein. J Biol Chem 1999; 274(35): 25061-8.
[http://dx.doi.org/10.1074/jbc.274.35.25061] [PMID: 10455185]
[51]
Bailey-Elkin BA, Knaap RCM, Kikkert M, Mark BL. Structure and Function of Viral Deubiquitinating Enzymes. J Mol Biol 2017; 429(22): 3441-70.
[http://dx.doi.org/10.1016/j.jmb.2017.06.010] [PMID: 28625850]
[52]
Wertheim JO, Chu DKW, Peiris JSM, Kosakovsky Pond SL, Poon LLM. A case for the ancient origin of coronaviruses. J Virol 2013; 87(12): 7039-45.
[http://dx.doi.org/10.1128/JVI.03273-12] [PMID: 23596293]
[53]
Hawkey PM, Bhagani S, Gillespie SH. Severe acute respiratory syndrome (SARS): Breath-taking progress. J Med Microbiol 2003; 52(8): 609-13.
[http://dx.doi.org/10.1099/jmm.0.05321-0] [PMID: 12867552]
[54]
Homepage, GERMS - Enabling the future. 2022. Avaialble From:http://www.germs.ro/en/Homepage/
[55]
Abdelrahman Z. Comparative Review of SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza A Respiratory Viruses. Front Immunol 2020; 11.
[56]
Redondo N, Zaldívar-López S, Garrido JJ, Montoya M. SARSCoV- 2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns Front Immunol 2021; 12http://dx.doi.org/10.3389/fimmu.2021.708264
[57]
Báez-Santos YM, St. John SE, Mesecar AD. The SARS-coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds. Antiviral Res 2015; 115(3): 21-38.
[58]
Yang X, Chen X, Bian G, et al. Proteolytic processing, deubiquitinase and interferon antagonist activities of Middle East respiratory syndrome coronavirus papain-like protease. J Gen Virol 2014; 95(3): 614-26.
[http://dx.doi.org/10.1099/vir.0.059014-0] [PMID: 24362959]
[59]
Yan S, Wu G. Spatial and temporal roles of SARS‐CoV PL pro —A snapshot. FASEB J 2021; 35(1): e21197.
[http://dx.doi.org/10.1096/fj.202002271] [PMID: 33368679]
[60]
van Kasteren PB, Bailey-Elkin BA, James TW, et al. Deubiquitinase function of arterivirus papain-like protease 2 suppresses the innate immune response in infected host cells. Proc Natl Acad Sci USA 2013; 110(9): E838-47.
[http://dx.doi.org/10.1073/pnas.1218464110] [PMID: 23401522]
[61]
The papain-like protease from the severe acute respiratory syndrome coronavirus is a deubiquitinating enzyme. 2005. Available From: https://journals.asm.org/doi/10.1128/JVI.79.24.15199-15208.2005
[62]
Devaraj SG, Wang N, Chen Z, et al. Regulation of IRF-3-dependent innate immunity by the papain-like protease domain of the severe acute respiratory syndrome coronavirus. J Biol Chem 2007; 282(44): 32208-21.
[http://dx.doi.org/10.1074/jbc.M704870200] [PMID: 17761676]
[63]
Chen ZJ. Ubiquitin signalling in the NF-κB pathway. Nat Cell Biol 2005; 7(8): 758-65.
[http://dx.doi.org/10.1038/ncb0805-758] [PMID: 16056267]
[64]
Békés M, Rut W, Kasperkiewicz P, et al. SARS hCoV papain-like protease is a unique Lys48 linkage-specific di-distributive deubiquitinating enzyme. Biochem J 2015; 468(2): 215-26.
[http://dx.doi.org/10.1042/BJ20141170] [PMID: 25764917]
[65]
Báez-Santos YM, Mielech AM, Deng X, Baker S, Mesecar AD. Catalytic function and substrate specificity of the papain-like protease domain of nsp3 from the Middle East respiratory syndrome coronavirus. J Virol 2014; 88(21): 12511-27.
[http://dx.doi.org/10.1128/JVI.01294-14] [PMID: 25142582]
[66]
Albini A, Di Guardo G, Noonan DM, Lombardo M. The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: Implications for ACE-inhibitor- and angiotensin II receptor blocker-based cardiovascular therapies. Intern Emerg Med 2020; 15(5): 759-66.
[http://dx.doi.org/10.1007/s11739-020-02364-6] [PMID: 32430651]
[67]
Jensen S, Thomsen AR. Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J Biol Chem 2005; 280(7): 5571-80.
[http://dx.doi.org/10.1074/jbc.M410592200] [PMID: 15579900]
[68]
Escriou N, Akira S, Chignard M, Si-Tahar M. Sensing of RNA Viruses: A Review of Innate Immune Receptors Involved in Recognizing RNA Virus Invasion. ASM J 2005; 86(6)
[69]
de Breyne S, Vindry C, Guillin O, et al. Translational control of coronaviruses. Nucleic Acids Res 2020; 48(22): 12502-22.
[http://dx.doi.org/10.1093/nar/gkaa1116] [PMID: 33264393]
[70]
Bailey-Elkin BA, Knaap RCM, Johnson GG, et al. Crystal structure of the Middle East respiratory syndrome coronavirus (MERS-CoV) papain-like protease bound to ubiquitin facilitates targeted disruption of deubiquitinating activity to demonstrate its role in innate immune suppression. J Biol Chem 2014; 289(50): 34667-82.
[http://dx.doi.org/10.1074/jbc.M114.609644] [PMID: 25320088]
[71]
Ghosh AK, Brindisi M, Shahabi D, Chapman ME, Mesecar AD. Drug Development and Medicinal Chemistry Efforts toward SARS‐Coronavirus and Covid‐19 Therapeutics. ChemMedChem 2020; 15(11): 907-32.
[http://dx.doi.org/10.1002/cmdc.202000223] [PMID: 32324951]
[72]
Lei J, Mesters JR, Drosten C, Anemüller S, Ma Q, Hilgenfeld R. Crystal structure of the papain-like protease of MERS coronavirus reveals unusual, potentially druggable active-site features. Antiviral Res 2014; 109: 72-82.
[http://dx.doi.org/10.1016/j.antiviral.2014.06.011] [PMID: 24992731]
[73]
Hilgenfeld R. From SARS to MERS: Crystallographic studies on coronaviral proteases enable antiviral drug design. The FEBS J 2014; 281(18): 4085-96.
[74]
Domingo-Calap P. Mechanisms of viral mutation. Cellular and Molecular Life Sciences 2016; 73: 4433-48.
[75]
Forster P, Forster L, Renfrew C, Forster M. Phylogenetic network analysis of SARS-CoV-2 genomes. Proc Natl Acad Sci USA 2020; 117(17): 9241-3.
[http://dx.doi.org/10.1073/pnas.2004999117] [PMID: 32269081]
[76]
Benvenuto D, Angeletti S, Giovanetti M, et al. Evolutionary analysis of SARS-CoV-2: How mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy. J Infect 2020; 81(1): e24-7.
[http://dx.doi.org/10.1016/j.jinf.2020.03.058] [PMID: 32283146]
[77]
Getov I, Petukh M, Alexov E. SAAFEC: Predicting the Effect of Single Point Mutations on Protein Folding Free Energy Using a Knowledge-Modified MM/PBSA Approach. Int J Mol Sci 2016; 17(4): 512.
[http://dx.doi.org/10.3390/ijms17040512] [PMID: 27070572]
[78]
Wei GW, Yin C, Hozumi Y. Decoding Asymptomatic COVID-19 Infection and Transmission. J Phys Chem Lett 2020; 11(23): 10007-15.
[79]
Cottam EM, Whelband MC, Wileman T. Coronavirus NSP6 restricts autophagosome expansion. Autophagy 2014; 10(8): 1426-41.
[http://dx.doi.org/10.4161/auto.29309] [PMID: 24991833]
[80]
Mielech AM, Kilianski A, Baez-Santos YM, Mesecar AD, Baker SC. MERS-CoV papain-like protease has deISGylating and deubiquitinating activities. Virology 2014; 450-451: 64-70.
[http://dx.doi.org/10.1016/j.virol.2013.11.040] [PMID: 24503068]
[81]
Amin SA, Banerjee S, Ghosh K, Gayen S, Jha T. Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors. Bioorg Med Chem 2021; 29: 115860.
[http://dx.doi.org/10.1016/j.bmc.2020.115860] [PMID: 33191083]
[82]
Zhao Y, Du X, Duan Y, et al. High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors. Protein Cell 2021; 12(11): 877-88.
[http://dx.doi.org/10.1007/s13238-021-00836-9] [PMID: 33864621]
[83]
Stasiulewicz A, Maksymiuk AW, Nguyen ML, Bełza B, Sulkowska JI. SARS-CoV-2 Papain-Like Protease Potential Inhibitors-In silico Quantitative Assessment. Int J Mol Sci 2021; 22(8): 3957.
[http://dx.doi.org/10.3390/ijms22083957] [PMID: 33921228]
[84]
Sadowski M, Suryadinata R, Tan AR, Roesley SNA, Sarcevic B. Protein monoubiquitination and polyubiquitination generate structural diversity to control distinct biological processes. IUBMB Life 2012; 64(2): 136-42.
[http://dx.doi.org/10.1002/iub.589] [PMID: 22131221]
[85]
Suresh B, Lee J, Kim H, Ramakrishna S. Regulation of pluripotency and differentiation by deubiquitinating enzymes. Cell Death Differ 2016; 23(8): 1257-64.
[http://dx.doi.org/10.1038/cdd.2016.53] [PMID: 27285106]
[86]
Villarroya-Beltri C, Guerra S, Sánchez-Madrid F. ISGylation – a key to lock the cell gates for preventing the spread of threats. J Cell Sci 2017; 130(18): jcs.205468.
[http://dx.doi.org/10.1242/jcs.205468] [PMID: 28842471]
[87]
Robinson SM, Tsueng G, Sin J, et al. Coxsackievirus B exits the host cell in shed microvesicles displaying autophagosomal markers. PLoS Pathog 2014; 10(4): e1004045.
[http://dx.doi.org/10.1371/journal.ppat.1004045] [PMID: 24722773]
[88]
Berryman S, Brooks E, Burman A. Foot-and-Mouth Disease Virus Induces Autophagosomes during Cell Entry via a Class III Phosphatidylinositol 3-Kinase-Independent Pathway. ASM J 2012; 86(23)
[89]
Prentice E, Jerome WG, Yoshimori T, Mizushima N, Denison MR. Coronavirus replication complex formation utilizes components of cellular autophagy. J Biol Chem 2004; 279(11): 10136-41.
[http://dx.doi.org/10.1074/jbc.M306124200] [PMID: 14699140]
[90]
Zhao Z, Thackray LB, Miller BC. Coronavirus Replication Does Not Require the Autophagy Gene ATG5. Autophagy 2007; 3(6): 581-5.
[91]
Ku B, Woo JS, Liang C, et al. Structural and biochemical bases for the inhibition of autophagy and apoptosis by viral BCL-2 of murine γ-herpesvirus 68. PLoS Pathog 2008; 4(2): e25.
[http://dx.doi.org/10.1371/journal.ppat.0040025] [PMID: 18248095]
[92]
Cuconati A, White E. Viral homologs of BCL-2: Role of apoptosis in the regulation of virus infection. Genes Dev 2002; 16(19): 2465-78.
[http://dx.doi.org/10.1101/gad.1012702] [PMID: 12368257]
[93]
Valera MS, de Armas-Rillo L, Barroso-González J, et al. The HDAC6/APOBEC3G complex regulates HIV-1 infectiveness by inducing Vif autophagic degradation. Retrovirology 2015; 12(1): 53.
[http://dx.doi.org/10.1186/s12977-015-0181-5] [PMID: 26105074]
[94]
Marin M, Rose KM, Kozak SL, Kabat D. HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nat Med 2003; 9(11): 1398-403.
[http://dx.doi.org/10.1038/nm946] [PMID: 14528301]
[95]
Tallóczy Z, Jiang W, Virgin HW IV, et al. Regulation of starvation- and virus-induced autophagy by the eIF2α kinase signaling pathway. Proc Natl Acad Sci USA 2002; 99(1): 190-5.
[http://dx.doi.org/10.1073/pnas.012485299] [PMID: 11756670]
[96]
Paul D, Bartenschlager R. Flaviviridae Replication Organelles: Oh, What a Tangled Web We Weave. Annu Rev Virol 2015; 2(1): 289-310.
[http://dx.doi.org/10.1146/annurev-virology-100114-055007] [PMID: 26958917]
[97]
Miller S, Kastner S, Krijnse-Locker J, Bühler S, Bartenschlager R. The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner. J Biol Chem 2007; 282(12): 8873-82.
[http://dx.doi.org/10.1074/jbc.M609919200] [PMID: 17276984]
[98]
Blázquez A-B, Martín-Acebes MA, Saiz J-C. Amino acid substitutions in the non-structural proteins 4A or 4B modulate the induction of autophagy in West Nile virus infected cells independently of the activation of the unfolded protein response. 2015. Available From:https://www.frontiersin.org/articles/10.3389/fmicb.2014.00797
[99]
Cortese M, Goellner S, Krijnse-Locker J, Acosta EG. Ultrastructural Characterization of Zika Virus Replication Factories. Cell Rep 2017; 18(9): 2013-23.

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