Skip to content
2000
Volume 6, Issue 4
  • ISSN: 2666-7967
  • E-ISSN: 2666-7975

Abstract

Purpose

To identify significant genes responsible for altering immune response in viral infections, including SARS, H1N1, Influenza, and Rhinovirus, as there are no previous studies that have analyzed these viral infections together.

Methods

Viral infection datasets pertaining to SARS, H1N1, Influenza, and Rhinovirus were obtained from the NCBI Gene Expression Omnibus. We have used three GEO datasets with accession numbers: GSE47962, GSE48466, and GSE71766. The Differentially Expressed Genes (DEG’s) were identified from each of the datasets, and then common DEGs were extracted. Protein-Protein-Interaction (PPI) network was constructed for the common DEGs obtained in all the virus datasets. Finally, we analyzed the PPI network to identify the hub genes that have high interconnectivity with other genes. The significantly enriched pathways are reported.

Results

By performing the comparative analysis, we identified 463 common DEG’s among the viral infection datasets under study. The highly interconnected PPI network constructed from these genes contained 3396 edges with an average node degree of 14.7 and an average local clustering coefficient of 0.406. There were 51 nodes with degree>50. The highest interconnected node, STAT1 had degree 113.

Conclusion

STAT 1 gene is identified as the most significant hub gene related to the immune response in all four viral infections, including SARS, H1N1, Influenza, and Rhinovirus. Its trivial role is already known in different viral infections, but being most significant in the four viruses together is a novel finding. It is thus identified as a central gene that is a potential therapeutic drug and vaccine target for viral infections.

Loading

Article metrics loading...

/content/journals/covid/10.2174/0126667975300308240703050733
2024-07-09
2025-10-03
Loading full text...

Full text loading...

References

  1. KakhkiR.K. KakhkiM.K. NeshaniA. COVID-19 target: A specific target for novel coronavirus detection.Gene Rep.20202010074010.1016/j.genrep.2020.100740
    [Google Scholar]
  2. ChenN. ZhouM. DongX. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus, pneumonia in Wuhan, China: A descriptive study.Lancet202039510223507513
    [Google Scholar]
  3. OludareA. Implications of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on the epidemiology of pediatric respiratory syncytial virus lection.Clin. Infect. Dis.202275S1S130S13510.1093/cid/ciac373
    [Google Scholar]
  4. DiamondM.S. KannegantiT.D. Innate immunity: the first line of defense against SARS-CoV-2.Nat. Immunol.202223216517610.1038/s41590‑021‑01091‑0
    [Google Scholar]
  5. RahimiF.S. AfaghiS. TarkiF.E. GoudarziK. AlamdariN.M. Viral outbreaks of SARS-CoV1, SARS-CoV2, MERS-CoV, influenza H1N1, and ebola in 21st Century; a comparative review of the pathogenesis and clinical characteristics. School of Medicine Students’.Journal20202318
    [Google Scholar]
  6. Cuadrado-PayánE. Montagud-MarrahiE. Torres-ElorzaM. SARS-CoV-2 and influenza virus co-infection.Lancet202039510236e8410.1016/S0140‑6736(20)31052‑7
    [Google Scholar]
  7. ChandrashekarD.S. AtharM. ManneU. VaramballyS. Comparative transcriptome analyses reveal genes associated with SARS-CoV-2 infection of human lung epithelial cells.Sci. Rep.20211111621210.1038/s41598‑021‑95733‑w
    [Google Scholar]
  8. MoniM.A. QuinnJ.M.W. SinmazN. SummersM.A. Gene expression profiling of SARS-CoV-2 infections reveal distinct primary lung cell and systemic immune infection responses that identify pathways relevant in COVID-19 disease.Brief. Bioinform.20212221324133710.1093/bib/bbaa376
    [Google Scholar]
  9. BibertS. GuexN. LourencoJ. Transcriptomic signature differences between SARS-CoV-2 and influenza virus infected patients.Front. Immunol.20211266616310.3389/fimmu.2021.666163
    [Google Scholar]
  10. BoscoA. WiehlerS. ProudD. Interferon regulatory factor 7 regulates airway epithelial cell responses to human rhinovirus infection.BMC Genomics20161717610.1186/s12864‑016‑2405‑z
    [Google Scholar]
  11. MitchellH.D. EisfeldA.J. SimsA.C. A network integration approach to predict conserved regulators related to pathogenicity of influenza and SARS-CoV respiratory viruses.PLoS One201387e6937410.1371/journal.pone.0069374
    [Google Scholar]
  12. SwetsM.C. RussellC.D. HarrisonE.M. SARS-CoV-2 co-infection with influenza viruses, respiratory syncytial virus, or adenoviruses.Lancet2022399103341463146410.1016/S0140‑6736(22)00383‑X
    [Google Scholar]
  13. PomaznoyM. HaB. PetersB. GOnet: a tool for interactive Gene Ontology analysis.BMC Bioinformatics201819147010.1186/s12859‑018‑2533‑3
    [Google Scholar]
  14. WangB. ZhengH. DongX. The identification distinct antiviral factors regulated influenza pandemic H1N1 infection.Int. J. Microbiol.2024202411210.1155/2024/6631882
    [Google Scholar]
  15. The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information.1988Available from: https://www.ncbi.nlm.nih.gov/ (accessed on 26-6-2024)
  16. GerlachR.L. CampJ.V. ChuY.K. JonssonC.B. Early host responses of seasonal and pandemic influenza A viruses in primary well-differentiated human lung epithelial cells.PLoS One2013811e7891210.1371/journal.pone.0078912
    [Google Scholar]
  17. KimT.K. Bheda-MalgeA. LinY. A systems approach to understanding human rhinovirus and influenza virus infection.Virology201548614615710.1016/j.virol.2015.08.014
    [Google Scholar]
  18. RStudio Team2020Available from: http://www.rstudio.com/ (accessed on 26-6-2024)
  19. GautierL. CopeL. BolstadB.M. IrizarryR.A. affy—analysis of Affymetrix GeneChip data at the probe level.Bioinformatics200420330731510.1093/bioinformatics/btg405
    [Google Scholar]
  20. RitchieM.E. PhipsonB. WuD. limma powers differential expression analyses for RNA-sequencing and microarray studies.Nucleic Acids Res.2015437e47e710.1093/nar/gkv007
    [Google Scholar]
  21. RameshP. VeerappapillaiS. KaruppasamyR. Gene expression profiling of corona virus microarray datasets to identify crucial targets in COVID-19 patients.Gene Rep.20212210098010.1016/j.genrep.2020.100980
    [Google Scholar]
  22. BenjaminiY. HochbergY. Controlling the false discovery rate: a practical and powerful approach to multiple testing.J. R. Stat. Soc. Series B Stat. Methodol.199557128930010.1111/j.2517‑6161.1995.tb02031.x
    [Google Scholar]
  23. SzklarczykD. GableA.L. LyonD. STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets.Nucleic Acids Res.201947D1D607D61310.1093/nar/gky1131
    [Google Scholar]
  24. TolomeoM. CavalliA. CascioA. STAT1 and Its Crucial Role in the Control of Viral Infections.Int. J. Mol. Sci.2022238409510.3390/ijms23084095
    [Google Scholar]
  25. Gilbert-GirardS. PiretJ. CarbonneauJ. HénautM. GoyetteN. BoivinG. Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses.bioRxiv2024.02.02.578538202410.1101/2024.02.02.578538
    [Google Scholar]
  26. BoonH. MeindersA.J. van HannenE.J. TersmetteM. SchaftenaarE. Comparative analysis of mortality in patients admitted with an infection with influenza A/B virus, respiratory syncytial virus, rhinovirus, metapneumovirus or SARS‐CoV‐2.Influenza Other Respir. Viruses2024181e1323710.1111/irv.13237
    [Google Scholar]
  27. Regina Malveste ItoC. SantosM.O. de Oliveira CunhaM. Rhinovirus infection and co-infection in children with severe acute respiratory infection during the COVID-19 pandemic period.Virulence2024151231087310.1080/21505594.2024.2310873
    [Google Scholar]
  28. Ghelfenstein-FerreiraT. SerrisA. SalmonaM. LanternierF. AlanioA. Revealing the hidden interplay: The unexplored relationship between fungi and viruses beyond HIV, SARS-CoV-2, and influenza.Med. Mycol.2024624myae02110.1093/mmy/myae021
    [Google Scholar]
  29. WadeS.F. DiouaraA.A.M. NgomB. ThiamF. DiaN. SARS-CoV-2 and other respiratory viruses in human olfactory pathophysiology.Microorganisms202412354010.3390/microorganisms12030540
    [Google Scholar]
  30. DeBERRYC MouS LinnekinD. Stat1 associates with c-kit and is activated in response to stem cell factor.Biochem. J.19973271738010.1042/bj3270073
    [Google Scholar]
  31. ZhangJ.J. VinkemeierU. GuW. ChakravartiD. HorvathC.M. DarnellJ.E.Jr Two contact regions between Stat1 and CBP/p300 in interferon γ signaling.Proc. Natl. Acad. Sci. USA19969326150921509610.1073/pnas.93.26.15092
    [Google Scholar]
  32. VidalM. RamanaC.V. DussoA.S. Stat1-vitamin D receptor interactions antagonize 1,25-dihydroxyvitamin D transcriptional activity and enhance stat1-mediated transcription.Mol. Cell. Biol.20022282777278710.1128/MCB.22.8.2777‑2787.2002
    [Google Scholar]
  33. TakedaA. HamanoS. YamanakaA. Cutting edge: role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment.J. Immunol.2003170104886489010.4049/jimmunol.170.10.4886
    [Google Scholar]
  34. LiX. LeungS. QureshiS. DarnellJ.E.Jr StarkG.R. Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha.J. Biol. Chem.1996271105790579410.1074/jbc.271.10.5790
    [Google Scholar]
  35. DumlerI. KopmannA. WagnerK. Urokinase induces activation and formation of Stat4 and Stat1-Stat2 complexes in human vascular smooth muscle cells.J. Biol. Chem.199927434240592406510.1074/jbc.274.34.24059
    [Google Scholar]
  36. FagerlundR. MelénK. KinnunenL. JulkunenI. Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin alpha 5.J. Biol. Chem.200227733300723007810.1074/jbc.M202943200
    [Google Scholar]
  37. XiaL. WangL. ChungA.S. Identification of both positive and negative domains within the epidermal growth factor receptor COOH-terminal region for signal transducer and activator of transcription (STAT) activation.J. Biol. Chem.200227734307163072310.1074/jbc.M202823200
    [Google Scholar]
  38. GunajeJ.J. Jayarama BhatG. Involvement of tyrosine phosphatase PTP1D in the inhibition of interleukin-6-induced Stat3 signaling by alpha-thrombin.Biochem. Biophys. Res. Commun.2001288125225710.1006/bbrc.2001.5759
    [Google Scholar]
  39. SpiekermannK. BiethahnS. Constitutive activation of STAT transcription factors in acute myelogenous leukemia.Eur. J. Haematol.2001672637110.1034/j.1600‑0609.2001.t01‑1‑00385.x
    [Google Scholar]
  40. Rincon-ArevaloH. AueA. RitterJ. Altered increase in STAT1 expression and phosphorylation in severe COVID‐19.Eur. J. Immunol.202252113814810.1002/eji.202149575
    [Google Scholar]
  41. OuchiT. LeeS.W. OuchiM. AaronsonS.A. HorvathC.M. Collaboration of signal transducer and activator of transcription 1 (STAT1) and BRCA1 in differential regulation of IFN-γ target genes.Proc. Natl. Acad. Sci. USA200097105208521310.1073/pnas.080469697
    [Google Scholar]
  42. UsachevaA. SmithR. MinshallR. The WD motif-containing protein receptor for activated protein kinase C (RACK1) is required for recruitment and activation of signal transducer and activator of transcription 1 through the type I interferon receptor.J. Biol. Chem.200127625229482295310.1074/jbc.M100087200
    [Google Scholar]
  43. UsachevaA. TianX. SandovalR. SalviD. LevyD. ColamoniciO.R. The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex.J. Immunol.200317162989299410.4049/jimmunol.171.6.2989
    [Google Scholar]
  44. MehtaP. McAuleyD.F. BrownM. SanchezE. TattersallR.S. MansonJ.J. COVID-19: consider cytokine storm syndromes and immunosuppression.Lancet2020395102291033103410.1016/S0140‑6736(20)30628‑0
    [Google Scholar]
  45. CascellaM. RajnikM. AleemA. Features, evaluation, and treatment of coronavirus (COVID-19).StatPearls.Treasure Island, FLStatPearls Publishing2022
    [Google Scholar]
  46. AdedokunK.A. OlarinmoyeA.O. MustaphaJ.O. KamorudeenR.T. A close look at the biology of SARS-CoV-2, and the potential influence of weather conditions and seasons on COVID-19 case spread.Infect. Dis. Poverty2020917710.1186/s40249‑020‑00688‑1
    [Google Scholar]
  47. NeufeldtC.J. CerikanB. CorteseM. SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB.Commun. Biol.2022514510.1038/s42003‑021‑02983‑5
    [Google Scholar]
  48. MatsuyamaT. KubliS.P. YoshinagaS.K. PfefferK. MakT.W. An aberrant STAT pathway is central to COVID-19.Cell Death Differ.202027123209322510.1038/s41418‑020‑00633‑7
    [Google Scholar]
  49. HashemiS.A. SafamaneshS. Ghasemzadeh-moghaddamH. GhafouriM. AzimianA. High prevalence of SARS‐CoV‐2 and influenza A virus (H1N1) coinfection in dead patients in Northeastern Iran.J. Med. Virol.20219321008101210.1002/jmv.26364
    [Google Scholar]
/content/journals/covid/10.2174/0126667975300308240703050733
Loading
/content/journals/covid/10.2174/0126667975300308240703050733
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.


  • Article Type:
    Research Article
Keyword(s): COVID-19; GEO; H1N1; influenza; limma; PPI; SARS; STAT 1
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test