Top

Published in:

01-08-2018 | Original Article

PCR array profiling of antiviral genes in human embryonic kidney cells expressing human coronavirus OC43 structural and accessory proteins

Authors: Meshal Beidas, Wassim Chehadeh

Published in: Archives of Virology | Issue 8/2018

Abstract

Human coronavirus OC43 (HCoV-OC43) is a respiratory virus that usually causes a common cold. However, it has the potential to cause severe infection in young children and immunocompromised adults. Both SARS-CoV and MERS-CoV were shown to express proteins with the potential to evade early innate immune responses. However, the ability of HCoV-OC43 to antagonise the intracellular antiviral defences has not yet been investigated. The potential role of the HCoV-OC43 structural (M and N) and accessory proteins (ns2a and ns5a) in the alteration of antiviral gene expression was investigated in this study. HCoV-OC43M, N, ns2a and ns5a proteins were expressed in human embryonic kidney 293 (HEK-293) cells before challenge with Sendai virus. The Human Antiviral Response PCR array was used to profile the antiviral gene expression in HEK-293 cells. Over 30 genes were downregulated in the presence of one of the HCoV-OC43 proteins, e.g. genes representing mitogen-activated protein kinases, toll-like receptors, interferons, interleukins, and signaling transduction proteins. Our findings suggest that similarly to SARS-CoV and MERS-CoV, HCoV-OC43 has the ability to downregulate the transcription of genes critical for the activation of different antiviral signaling pathways. Further studies are needed to confirm the role of HCoV-OC43 structural and accessory proteins in antagonising antiviral gene expression.

Cavanagh D (1997) Nidovirales: a new order comprising Coronaviridae and Arteriviridae. Arch Virol 142:629–633PubMed

Vijgen L, Keyaerts E, Lemey P et al (2005) Circulation of genetically distinct contemporary human coronavirus OC43 strains. Virology 337:85–92. https://doi.org/10.1016/j.virol.2005.04.010 CrossRefPubMed

Larson HE, Reed SE, Tyrrell DA (1980) Isolation of rhinoviruses and coronaviruses from 38 colds in adults. J Med Virol 5:221–229CrossRefPubMed

Lepiller Q, Barth H, Lefebvre F et al (2013) High incidence but low burden of coronaviruses and preferential associations between respiratory viruses. J Clin Microbiol 51:3039–3046. https://doi.org/10.1128/JCM.01078-13 CrossRefPubMedPubMedCentral

Razuri H, Malecki M, Tinoco Y et al (2015) Human coronavirus-associated influenza-like illness in the community setting in Peru. Am J Trop Med Hyg 93:1038–1040. https://doi.org/10.4269/ajtmh.15-0271 CrossRefPubMedPubMedCentral

Talbot HK, Shepherd BE, Crowe JEJ et al (2009) The pediatric burden of human coronaviruses evaluated for twenty years. Pediatr Infect Dis J 28:682–687. https://doi.org/10.1097/INF.0b013e31819d0d27 CrossRefPubMedPubMedCentral

Geller C, Varbanov M, Duval RE (2012) Human coronaviruses: insights into environmental resistance and its influence on the development of new antiseptic strategies. Viruses 4:3044–3068. https://doi.org/10.3390/v4113044 CrossRefPubMedPubMedCentral

Arbour N, Cote G, Lachance C et al (1999) Acute and persistent infection of human neural cell lines by human coronavirus OC43. J Virol 73:3338–3350PubMedPubMedCentral

Arbour N, Day R, Newcombe J, Talbot PJ (2000) Neuroinvasion by human respiratory coronaviruses. J Virol 74:8913–8921CrossRefPubMedPubMedCentral

10.

Yeh EA, Collins A, Cohen ME et al (2004) Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics 113:e73–e76CrossRefPubMed

11.

Morfopoulou S, Brown JR, Davies EG et al (2016) Human coronavirus OC43 associated with fatal encephalitis. N Engl J Med 375:497–498. https://doi.org/10.1056/NEJMc1509458 CrossRefPubMed

12.

Ye J, Zhang B, Xu J et al (2007) Molecular pathology in the lungs of severe acute respiratory syndrome patients. Am J Pathol 170:538–545. https://doi.org/10.2353/ajpath.2007.060469 CrossRefPubMedPubMedCentral

13.

Fang X, Gao J, Zheng H et al (2007) The membrane protein of SARS-CoV suppresses NF-kappaB activation. J Med Virol 79:1431–1439. https://doi.org/10.1002/jmv.20953 CrossRefPubMed

14.

Kopecky-Bromberg SA, Martinez-Sobrido L, Frieman M et al (2007) Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. J Virol 81:548–557. https://doi.org/10.1128/jvi.01782-06 CrossRefPubMed

15.

Siu K-L, Chan C-P, Kok K-H et al (2014) Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. Cell Mol Immunol 11:141–149. https://doi.org/10.1038/cmi.2013.61 CrossRefPubMedPubMedCentral

16.

Niemeyer D, Zillinger T, Muth D et al (2013) Middle East respiratory syndrome coronavirus accessory protein 4a is a type I interferon antagonist. J Virol 87:12489–12495. https://doi.org/10.1128/JVI.01845-13 CrossRefPubMedPubMedCentral

17.

Yang Y, Zhang L, Geng H et al (2013) The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists. Protein Cell 4:951–961. https://doi.org/10.1007/s13238-013-3096-8 CrossRefPubMedPubMedCentral

18.

Assiri A, McGeer A, Perl TM et al (2013) Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med 369:407–416. https://doi.org/10.1056/NEJMoa1306742 CrossRefPubMedPubMedCentral

19.

Assiri A, Al-Tawfiq JA, Al-Rabeeah AA et al (2013) Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis 13:752–761. https://doi.org/10.1016/S1473-3099(13)70204-4 CrossRefPubMed

20.

Lee HKK, Tso EYK, Chau TN et al (2003) Asymptomatic severe acute respiratory syndrome-associated coronavirus infection. Emerg Infect Dis 9:1491–1492CrossRefPubMedPubMedCentral

21.

Li G, Zhao Z, Chen L, Zhou Y (2003) Mild severe acute respiratory syndrome. Emerg Infect Dis 9:1182–1183CrossRefPubMedPubMedCentral

22.

Lai FW, Stephenson KB, Mahony J, Lichty BD (2014) Human coronavirus OC43 nucleocapsid protein binds microRNA 9 and potentiates NF-κB activation. J Virol 88:54–65. https://doi.org/10.1128/JVI.02678-13 CrossRefPubMedPubMedCentral

23.

Zhao X, Guo F, Liu F et al (2014) Interferon induction of IFITM proteins promotes infection by human coronavirus OC43. Proc Natl Acad Sci USA 111:1–6. https://doi.org/10.1073/pnas.1320856111 CrossRef

24.

Desforges M, Desjardins J, Zhang C, Talbot PJ (2013) The acetyl-esterase activity of the hemagglutinin-esterase protein of human coronavirus OC43 strongly enhances the production of infectious. Virus 87:3097–3107. https://doi.org/10.1128/JVI.02699-12 CrossRef

25.

Lee HK, Tang JWT, Kong DHL, Koay ESC (2013) Simplified large-scale sanger genome sequencing for influenza A/H3N2 Virus. PLoS One. https://doi.org/10.1371/journal.pone.0064785 CrossRefPubMedPubMedCentral

26.

Hatada E, Fukuda R (1992) Binding of influenza A virus NS1 protein to dsRNA in vitro. J Gen Virol 73(Pt 12):3325–3329. https://doi.org/10.1099/0022-1317-73-12-3325 CrossRefPubMed

27.

Bergmann M, Garcia-Sastre A, Carnero E et al (2000) Influenza virus NS1 protein counteracts PKR-mediated inhibition of replication. J Virol 74:6203–6206CrossRefPubMedPubMedCentral

28.

Lu Y, Wambach M, Katze MG, Krug RM (1995) Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the elF-2 translation initiation factor. Virology 214:222–228CrossRefPubMed

29.

McBride R, Fielding BC (2012) The role of severe acute respiratory syndrome (SARS)-coronavirus accessory proteins in virus pathogenesis. Viruses 4:2902–2923. https://doi.org/10.3390/v4112902 CrossRefPubMedPubMedCentral

30.

Zhang R, Wang K, Ping X et al (2015) The ns12.9 accessory protein of human coronavirus OC43 is a viroporin involved in virion morphogenesis and pathogenesis. J Virol 89:11383–11395. https://doi.org/10.1128/JVI.01986-15 CrossRefPubMedPubMedCentral

31.

Koetzner CA, Kuo L, Goebel SJ et al (2010) Accessory protein 5a is a major antagonist of the antiviral action of interferon against murine coronavirus. J Virol 84:8262–8274. https://doi.org/10.1128/JVI.00385-10 CrossRefPubMedPubMedCentral

32.

Das KC, Muniyappa H (2010) c-Jun-NH2 terminal kinase (JNK)-mediates AP-1 activation by thioredoxin: phosphorylation of cJun, JunB, and Fra-1. Mol Cell Biochem 337:53–63. https://doi.org/10.1007/s11010-009-0285-0 CrossRefPubMed

33.

Krishna M, Narang H (2008) The complexity of mitogen-activated protein kinases (MAPKs) made simple. Cell Mol Life Sci 65:3525–3544. https://doi.org/10.1007/s00018-008-8170-7 CrossRefPubMed

34.

Locker JK, Rose JK, Horzinek MC, Rottier PJ (1992) Membrane assembly of the triple-spanning coronavirus M protein. Individual transmembrane domains show preferred orientation. J Biol Chem 267:21911–21918PubMed

35.

Lui P-Y, Wong L-YR, Fung C-L et al (2016) Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3. Emerg Microbes Infect 5:e39. https://doi.org/10.1038/emi.2016.33 CrossRefPubMedPubMedCentral

36.

Mak TW, Yeh W-C (2002) Signaling for survival and apoptosis in the immune system. Arthritis Res 4:S243. https://doi.org/10.1186/ar569 CrossRefPubMedPubMedCentral

37.

Parker MM, Masters PS (1990) Sequence comparison of the N genes of five strains of the coronavirus mouse hepatitis virus suggests a three domain structure for the nucleocapsid protein. Virology 179:463–468CrossRefPubMed

38.

Kuo L, Masters PS (2002) Genetic evidence for a structural interaction between the carboxy termini of the membrane and nucleocapsid proteins of mouse hepatitis virus. J Virol 76:4987–4999CrossRefPubMedPubMedCentral

39.

Yan X, Hao Q, Mu Y et al (2006) Nucleocapsid protein of SARS-CoV activates the expression of cyclooxygenase-2 by binding directly to regulatory elements for nuclear factor-kappa B and CCAAT/enhancer binding protein. Int J Biochem Cell Biol 38:1417–1428. https://doi.org/10.1016/j.biocel.2006.02.003 CrossRefPubMed

40.

Perlman S, Netland J (2009) Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol 7:439–450. https://doi.org/10.1038/nrmicro2147 CrossRefPubMedPubMedCentral

41.

Dai L, Aye Thu C, Liu X-Y et al (2012) TAK1, more than just innate immunity. IUBMB Life 64:825–834. https://doi.org/10.1002/iub.1078 CrossRefPubMed

42.

Jiang Z, Zamanian-Daryoush M, Nie H et al (2003) Poly(I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFkappa B and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3-TRAF6-TAK1-TAB2-PKR. J Biol Chem 278:16713–16719. https://doi.org/10.1074/jbc.M300562200 CrossRefPubMed

43.

Ogolla PS, Portillo J-AC, White CL et al (2013) The protein kinase double-stranded RNA-dependent (PKR) enhances protection against disease cause by a non-viral pathogen. PLoS Pathog 9:e1003557. https://doi.org/10.1371/journal.ppat.1003557 CrossRefPubMedPubMedCentral

44.

Cheung CY, Poon LLM, Ng IHY et al (2005) Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. J Virol 79:7819–7826. https://doi.org/10.1128/JVI.79.12.7819-7826.2005 CrossRefPubMedPubMedCentral

45.

Lau SKP, Lau CCY, Chan K-H et al (2013) Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment. J Gen Virol 94:2679–2690. https://doi.org/10.1099/vir.0.055533-0 CrossRefPubMed

Title: PCR array profiling of antiviral genes in human embryonic kidney cells expressing human coronavirus OC43 structural and accessory proteins
Authors: Meshal Beidas
Wassim Chehadeh
Publication date: 01-08-2018
Publisher: Springer Vienna
Published in: Archives of Virology / Issue 8/2018
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-018-3832-8

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

PCR array profiling of antiviral genes in human embryonic kidney cells expressing human coronavirus OC43 structural and accessory proteins

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 8/2018

Isolation and characterization of a group of new Proteus bacteriophages

Surveillance of HIV-1 drug resistance in Xinjiang: high prevalence of K103N in treatment-naïve individuals

Viruses do not have polythetic properties; species are polythetic classes and do not have any properties

Taxonomy of the order Mononegavirales: update 2018

Sequencing, genome analysis and host range of a novel Ralstonia phage, RsoP1EGY, isolated in Egypt

Molecular characterization of avipoxviruses circulating in Mozambique, 2016-2018

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page