1887

Abstract

Reactive oxygen species (ROS) are chemically active species which are involved in maintaining cellular and signalling processes at physiological concentrations. Therefore, cellular components that regulate redox balance are likely to play a crucial role in viral life-cycle either as promoters of viral replication or with antiviral functions. Zinc is an essential micronutrient associated with anti-oxidative systems and helps in maintaining a balanced cellular redox state. Here, we show that zinc chelation leads to induction of reactive oxygen species (ROS) in epithelial cells and addition of zinc restores ROS levels to basal state. Addition of ROS (HO) inhibited dengue virus (DENV) infection in a dose-dependent manner indicating that oxidative stress has adverse effects on DENV infection. ROS affects early stages of DENV replication as observed by quantitation of positive and negative strand viral RNA. We observed that addition of ROS specifically affected viral titres of positive strand RNA viruses. We further demonstrate that ROS specifically altered SEC31A expression at the ER suggesting a role for SEC31A-mediated pathways in the life-cycle of positive strand RNA viruses and provides an opportunity to identify drug targets regulating oxidative stress responses for antiviral development.

Funding
This study was supported by the:
  • The Wellcome Trust DBT India Alliance (Award IA/S/14/1/501291)
    • Principle Award Recipient: GuruprasadR Medigeshi
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/content/journal/jgv/10.1099/jgv.0.001596
2021-04-27
2021-05-17
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References

  1. Dale DC, Boxer L, Liles WC. The phagocytes: neutrophils and monocytes. Blood 2008; 112:935–945 [CrossRef][PubMed]
    [Google Scholar]
  2. Klebanoff SJ. Myeloperoxidase: friend and foe. J Leukoc Biol 2005; 77:598–625 [CrossRef][PubMed]
    [Google Scholar]
  3. Brieger K, Schiavone S, Krause K-H, Krause K-H. Reactive oxygen species: from health to disease. Swiss Med Wkly 2012; 142:w13659 [CrossRef][PubMed]
    [Google Scholar]
  4. Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F et al. Oxidative stress: harms and benefits for human health. Oxid Med Cell Longev 2017; 2017:841676313 [CrossRef][PubMed]
    [Google Scholar]
  5. Israël N, Gougerot-Pocidalo MA. Oxidative stress in human immunodeficiency virus infection. Cell Mol Life Sci 1997; 53:864–870 [CrossRef][PubMed]
    [Google Scholar]
  6. Imai Y, Kuba K, Neely GG, Yaghubian-Malhami R, Perkmann T et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 2008; 133:235–249 [CrossRef][PubMed]
    [Google Scholar]
  7. Komaravelli N, Ansar M, Garofalo RP, Casola A. Respiratory syncytial virus induces NRF2 degradation through a promyelocytic leukemia protein - ring finger protein 4 dependent pathway. Free Radic Biol Med 2017; 113:494–504 [CrossRef][PubMed]
    [Google Scholar]
  8. Vijay R, Hua X, Meyerholz DK, Miki Y, Yamamoto K et al. Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection. J Exp Med 2015; 212:1851–1868 [CrossRef][PubMed]
    [Google Scholar]
  9. Nasi A, McArdle S, Gaudernack G, Westman G, Melief C et al. Reactive oxygen species as an initiator of toxic innate immune responses in retort to SARS-CoV-2 in an ageing population, consider N-acetylcysteine as early therapeutic intervention. Toxicol Rep 2020; 7:768–771 [CrossRef][PubMed]
    [Google Scholar]
  10. Gong G, Waris G, Tanveer R, Siddiqui A. Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B. Proc Natl Acad Sci U S A 2001; 98:9599–9604 [CrossRef][PubMed]
    [Google Scholar]
  11. Choi J, Lee KJ, Zheng Y, Yamaga AK, Lai MMC et al. Reactive oxygen species suppress hepatitis C virus RNA replication in human hepatoma cells. Hepatology 2004; 39:81–89 [CrossRef][PubMed]
    [Google Scholar]
  12. Zhang Z, Rong L, YP L, Viruses F. And oxidative stress: implications for viral pathogenesis. Oxid Med Cell Longev 2019; 2019:1409582
    [Google Scholar]
  13. Olagnier D, Peri S, Steel C, van Montfoort N, Chiang C et al. Cellular oxidative stress response controls the antiviral and apoptotic programs in dengue virus-infected dendritic cells. PLoS Pathog 2014; 10:e1004566 [CrossRef][PubMed]
    [Google Scholar]
  14. Singla M, Kar M, Sethi T, Kabra SK, Lodha R et al. Immune response to dengue virus infection in pediatric patients in New Delhi, India--association of viremia, inflammatory mediators and monocytes with disease severity. PLoS Negl Trop Dis 2016; 10::e0004497 [CrossRef][PubMed]
    [Google Scholar]
  15. Kar M, Singla M, Chandele A, Kabra SK, Lodha R et al. Dengue virus entry and replication does not lead to productive infection in platelets. Open Forum Infect Dis 2017; 4:ofx051 [CrossRef][PubMed]
    [Google Scholar]
  16. Organization WH Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control, New Edition. Geneva: WHO Guidelines Approved by the Guidelines Review Committee; 2009
    [Google Scholar]
  17. Kar M, Khan NA, Panwar A, Bais SS, Basak S et al. Zinc chelation specifically inhibits early stages of dengue virus replication by activation of NF-κB and induction of antiviral response in epithelial cells. Front Immunol 2019; 10:2347 [CrossRef][PubMed]
    [Google Scholar]
  18. Medigeshi GR, Kumar R, Dhamija E, Agrawal T, Kar M. N-Desmethylclozapine, fluoxetine, and salmeterol inhibit Postentry stages of the dengue virus life cycle. Antimicrob Agents Chemother 2016; 60:6709–6718 [CrossRef][PubMed]
    [Google Scholar]
  19. Anantharaj A, Gujjar S, Kumar S, Verma N, Wangchuk J et al. Kinetics of viral load, immunological mediators and characterization of a SARS-CoV-2 isolate in mild COVID-19 patients during acute phase of infection. medRxiv 2020
    [Google Scholar]
  20. Khan NA, Singla M, Samal S, Lodha R, Medigeshi GR. Respiratory syncytial virus-induced oxidative stress leads to an increase in labile zinc pools in lung epithelial cells. mSphere 2020; 5:e00447–20 [CrossRef][PubMed]
    [Google Scholar]
  21. Haridas V, Rajgokul KS, Sadanandan S, Agrawal T, Sharvani V et al. Bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block Japanese encephalitis virus replication. PLoS Negl Trop Dis 2013; 7:e2005 [CrossRef][PubMed]
    [Google Scholar]
  22. Reshi ML, Su Y-C, Hong J-R. Rna viruses: ROS-mediated cell death. Int J Cell Biol 2014; 2014:46745216 [CrossRef][PubMed]
    [Google Scholar]
  23. Selisko B, Wang C, Harris E, Canard B. Regulation of flavivirus RNA synthesis and replication. Curr Opin Virol 2014; 9:74–83 [CrossRef][PubMed]
    [Google Scholar]
  24. Lu Q, Haragopal H, Slepchenko KG, Stork C, Li YV. Intracellular zinc distribution in mitochondria, ER and the Golgi apparatus. Int J Physiol Pathophysiol Pharmacol 2016; 8:35–43[PubMed]
    [Google Scholar]
  25. Qin Y, Dittmer PJ, Park JG, Jansen KB, Palmer AE. Measuring steady-state and dynamic endoplasmic reticulum and Golgi Zn2+ with genetically encoded sensors. Proc Natl Acad Sci U S A 2011; 108:7351–7356 [CrossRef]
    [Google Scholar]
  26. Gullberg RC, Jordan Steel J, Moon SL, Soltani E, Geiss BJ. Oxidative stress influences positive strand RNA virus genome synthesis and capping. Virology 2015; 475:219–229 [CrossRef][PubMed]
    [Google Scholar]
  27. Schwarz KB. Oxidative stress during viral infection: a review. Free Radic Biol Med 1996; 21:641–649 [CrossRef][PubMed]
    [Google Scholar]
  28. Suzuki T, Katsumata S-I, Matsuzaki H, Suzuki K. Dietary zinc deficiency induces oxidative stress and promotes tumor necrosis factor-α- and interleukin-1β-induced RANKL expression in rat bone. J Clin Biochem Nutr 2016; 58:122–129 [CrossRef][PubMed]
    [Google Scholar]
  29. Salonen A, Ahola T, Kääriäinen L. Viral RNA replication in association with cellular membranes. Curr Top Microbiol Immunol 2005; 285:139–173 [CrossRef][PubMed]
    [Google Scholar]
  30. Tongmuang N, Yasamut U, Songprakhon P, Dechtawewat T, Malakar S et al. Coat protein complex I facilitates dengue virus production. Virus Res 2018; 250:13–20 [CrossRef][PubMed]
    [Google Scholar]
  31. Trahey M, Oh HS, Cameron CE, Hay JC. Poliovirus infection transiently increases COPII vesicle budding. J Virol 2012; 86:9675–9682 [CrossRef][PubMed]
    [Google Scholar]
  32. Vonderstein K, Nilsson E, Hubel P, Nygård Skalman L, Upadhyay A et al. Viperin targets flavivirus virulence by inducing assembly of noninfectious capsid particles. J Virol 2018; 92: 01 01 2018 [CrossRef][PubMed]
    [Google Scholar]
  33. Yamayoshi S, Noda T, Ebihara H, Goto H, Morikawa Y et al. Ebola virus matrix protein VP40 uses the COPII transport system for its intracellular transport. Cell Host Microbe 2008; 3:168–177 [CrossRef][PubMed]
    [Google Scholar]
  34. Zhang N, Zhang L. Key components of COPI and COPII machineries are required for chikungunya virus replication. Biochem Biophys Res Commun 2017; 493:1190–1196 [CrossRef][PubMed]
    [Google Scholar]
  35. Somasekharan SP, Zhang F, Saxena N, Huang JN, Kuo I-C et al. G3BP1-linked mRNA partitioning supports selective protein synthesis in response to oxidative stress. Nucleic Acids Res 2020; 48:6855–6873 [CrossRef][PubMed]
    [Google Scholar]
  36. Kaminski MM, Sauer SW, Klemke C-D, Süss D, Okun JG et al. Mitochondrial reactive oxygen species control T cell activation by regulating IL-2 and IL-4 expression: mechanism of ciprofloxacin-mediated immunosuppression. J Immunol 2010; 184:4827–4841 [CrossRef][PubMed]
    [Google Scholar]
  37. Abimannan T, Peroumal D, Parida JR, Barik PK, Padhan P et al. Oxidative stress modulates the cytokine response of differentiated Th17 and Th1 cells. Free Radic Biol Med 2016; 99:352–363 [CrossRef][PubMed]
    [Google Scholar]
  38. Choi HK, Kim TH, Jhon G-J, Lee SY. Reactive oxygen species regulate M-CSF-induced monocyte/macrophage proliferation through SHP1 oxidation. Cell Signal 2011; 23:1633–1639 [CrossRef][PubMed]
    [Google Scholar]
  39. Steevels TAM, van Avondt K, Westerlaken GHA, Stalpers F, Walk J et al. Signal inhibitory receptor on leukocytes-1 (SIRL-1) negatively regulates the oxidative burst in human phagocytes. Eur J Immunol 2013; 43:1297–1308 [CrossRef][PubMed]
    [Google Scholar]
  40. Finsterbusch M, Hall P, Li A, Devi S, Westhorpe CLV et al. Patrolling monocytes promote intravascular neutrophil activation and glomerular injury in the acutely inflamed glomerulus. Proc Natl Acad Sci U S A 2016; 113:E5172–E5181 [CrossRef][PubMed]
    [Google Scholar]
  41. Chan KR, Gan ES, Chan CYY, Liang C, Low JZH et al. Metabolic perturbations and cellular stress underpin susceptibility to symptomatic live-attenuated yellow fever infection. Nat Med 2019; 25:1218–1224 [CrossRef][PubMed]
    [Google Scholar]
  42. Gil L, Martínez G, Tápanes R, Castro O, González D et al. Oxidative stress in adult dengue patients. Am J Trop Med Hyg 2004; 71:652–657 [CrossRef][PubMed]
    [Google Scholar]
  43. Soundravally R, Sankar P, Bobby Z, Hoti SL. Oxidative stress in severe dengue viral infection: association of thrombocytopenia with lipid peroxidation. Platelets 2008; 19:447–454 [CrossRef][PubMed]
    [Google Scholar]
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