1887

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Volume 98, Issue 3

Viral dependence on cellular ion channels – an emerging anti-viral target? Free

Abstract

The broad range of cellular functions governed by ion channels represents an attractive target for viral manipulation. Indeed, modulation of host cell ion channel activity by viral proteins is being increasingly identified as an important virus–host interaction. Recent examples have demonstrated that virion entry, virus egress and the maintenance of a cellular environment conducive to virus persistence are, in part, dependent on virus manipulation of ion channel activity. Most excitingly, evidence has emerged that targeting ion channels pharmacologically can impede virus life cycles. Here, we discuss current examples of virus–ion channel interactions and the potential of targeting ion channel function as a new, pharmacologically safe and broad-ranging anti-viral therapeutic strategy.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): cell biology , ion channel , pathogenesis and virus
© 2017 The Authors
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2017-03-01
2024-04-20
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References

  1. Yu FH, Yarov-Yarovoy V, Gutman GA, Catterall WA. Overview of molecular relationships in the voltage-gated ion channel superfamily. Pharmacol Rev 2005; 57:387–395 [View Article][PubMed]
     [Google Scholar]
  2. Balse E, Steele DF, Abriel H, Coulombe A, Fedida D et al. Dynamic of ion channel expression at the plasma membrane of cardiomyocytes. Physiol Rev 2012; 92:1317–1358 [View Article][PubMed]
     [Google Scholar]
  3. Kim JB. Channelopathies. Korean J Pediatr 2014; 57:1–18 [View Article][PubMed]
     [Google Scholar]
  4. O'Grady SM, Lee SY. Chloride and potassium channel function in alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol 2003; 284:L689–L700 [View Article][PubMed]
     [Google Scholar]
  5. Bardou O, Trinh NT, Brochiero E. Molecular diversity and function of K+ channels in airway and alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol 2009; 296:L145–L155 [View Article][PubMed]
     [Google Scholar]
  6. Roger S, Gillet L, Le Guennec JY, Besson P. Voltage-gated sodium channels and cancer: is excitability their primary role?. Front Pharmacol 2015; 6:152 [View Article][PubMed]
     [Google Scholar]
  7. Schwab A, Stock C. Ion channels and transporters in tumour cell migration and invasion. Philos Trans R Soc Lond B Biol Sci 2014; 369:20130102 [View Article][PubMed]
     [Google Scholar]
  8. Hübner CA, Jentsch TJ. Ion channel diseases. Hum Mol Genet 2002; 11:2435–2445 [View Article][PubMed]
     [Google Scholar]
  9. Royle J, Dobson SJ, Müller M, Macdonald A. Emerging roles of viroporins encoded by dna viruses: novel targets for antivirals?. Viruses 2015; 7:5375–5387 [View Article][PubMed]
     [Google Scholar]
  10. Sze CW, Tan YJ. Viral membrane channels: role and function in the virus life cycle. Viruses 2015; 7:3261–3284 [View Article][PubMed]
     [Google Scholar]
  11. Gehring G, Rohrmann K, Atenchong N, Mittler E, Becker S et al. The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry. J Antimicrob Chemother 2014; 69:2123–2131 [View Article][PubMed]
     [Google Scholar]
  12. Sakurai Y, Kolokoltsov AA, Chen CC, Tidwell MW, Bauta WE et al. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment. Science 2015; 347:995–998 [View Article][PubMed]
     [Google Scholar]
  13. Hover S, King B, Hall B, Loundras EA, Taqi H et al. Modulation of potassium channels inhibits bunyavirus infection. J Biol Chem 2016; 291:3411–3422 [View Article][PubMed]
     [Google Scholar]
  14. Zheng K, Chen M, Xiang Y, Ma K, Jin F et al. Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB. Biochem Biophys Res Commun 2014; 446:990–996 [View Article][PubMed]
     [Google Scholar]
  15. Giannini C, Bréchot C. Hepatitis C virus biology. Cell Death Differ 2003; 10:S27–S38 [View Article][PubMed]
     [Google Scholar]
  16. Mankouri J, Dallas ML, Hughes ME, Griffin SD, Macdonald A et al. Suppression of a pro-apoptotic K+ channel as a mechanism for hepatitis C virus persistence. Proc Natl Acad Sci USA 2009; 106:15903–15908 [View Article][PubMed]
     [Google Scholar]
  17. Redman PT, He K, Hartnett KA, Jefferson BS, Hu L et al. Apoptotic surge of potassium currents is mediated by p38 phosphorylation of Kv2.1. Proc Natl Acad Sci USA 2007; 104:3568–3573 [View Article][PubMed]
     [Google Scholar]
  18. Norris CA, He K, Springer MG, Hartnett KA, Horn JP et al. Regulation of neuronal proapoptotic potassium currents by the hepatitis C virus nonstructural protein 5a. J Neurosci 2012; 32:8865–8870 [View Article][PubMed]
     [Google Scholar]
  19. Igloi Z, Mohl BP, Lippiat JD, Harris M, Mankouri J. Requirement for chloride channel function during the hepatitis C virus life cycle. J Virol 2015; 89:4023–4029 [View Article][PubMed]
     [Google Scholar]
  20. Choi B, Fermin CD, Comardelle AM, Haislip AM, Voss TG et al. Alterations in intracellular potassium concentration by HIV-1 and SIV Nef. Virol J 2008; 5:60 [View Article][PubMed]
     [Google Scholar]
  21. Herrmann M, Ruprecht K, Sauter M, Martinez J, van Heteren P et al. Interaction of human immunodeficiency virus gp120 with the voltage-gated potassium channel BEC1. FEBS Lett 2010; 584:3513–3518 [View Article][PubMed]
     [Google Scholar]
  22. Kort JJ, Jalonen TO. The nef protein of the human immunodeficiency virus type 1 (HIV-1) inhibits a large-conductance potassium channel in human glial cells. Neurosci Lett 1998; 251:1–4 [View Article][PubMed]
     [Google Scholar]
  23. Hsu K, Han J, Shinlapawittayatorn K, Deschenes I, Marbán E. Membrane potential depolarization as a triggering mechanism for Vpu-mediated HIV-1 release. Biophys J 2010; 99:1718–1725 [View Article][PubMed]
     [Google Scholar]
  24. Strebel K. HIV-1 Vpu: putting a channel to the TASK. Mol Cell 2004; 14:150–152[PubMed] [Crossref]
     [Google Scholar]
  25. Hsu K, Seharaseyon J, Dong P, Bour S, Marbán E. Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel. Mol Cell 2004; 14:259–267 [View Article][PubMed]
     [Google Scholar]
  26. Alkhalil A, Hammamieh R, Hardick J, Ichou MA, Jett M et al. Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host–virus interactions. Virol J 2010; 7:173 [View Article][PubMed]
     [Google Scholar]
  27. Dellis O, Arbabian A, Papp B, Rowe M, Joab I et al. Epstein–Barr virus latent membrane protein 1 increases calcium influx through store-operated channels in B lymphoid cells. J Biol Chem 2011; 286:18583–18592 [View Article][PubMed]
     [Google Scholar]
  28. Biasiotto R, Aguiari P, Rizzuto R, Pinton P, D'Agostino DM et al. The p13 protein of human T cell leukemia virus type 1 (HTLV-1) modulates mitochondrial membrane potential and calcium uptake. Biochim Biophys Acta 2010; 1797:945–951 [View Article][PubMed]
     [Google Scholar]
  29. Stauffer EK, Ziegler RJ. Loss of functional voltage-gated sodium channels in persistent mumps virus-infected PC12 cells. J Gen Virol 1989; 70:749–754 [View Article][PubMed]
     [Google Scholar]
  30. Kennedy PG, Montague P, Scott F, Grinfeld E, Ashrafi GH et al. Varicella-zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line. PLoS One 2013; 8:e51570 [View Article][PubMed]
     [Google Scholar]
  31. Iwata M, Komori S, Unno T, Minamoto N, Ohashi H. Modification of membrane currents in mouse neuroblastoma cells following infection with rabies virus. Br J Pharmacol 1999; 126:1691–1698 [View Article][PubMed]
     [Google Scholar]
  32. Rosenblum LA, Coplan JD, Friedman S, Bassoff T. Dose–response effects of oral yohimbine in unrestrained primates. Biol Psychiatry 1991; 29:647–657 [View Article][PubMed]
     [Google Scholar]
  33. Starke K, Göthert M, Kilbinger H. Modulation of neurotransmitter release by presynaptic autoreceptors. Physiol Rev 1989; 69:864–989[PubMed] [Crossref]
     [Google Scholar]
  34. Visentin S, Renzi M, Levi G. Altered outward-rectifying K+ current reveals microglial activation induced by HIV-1 Tat protein. Glia 2001; 33:181–190 [View Article][PubMed]
     [Google Scholar]
  35. Liu J, Xu P, Collins C, Liu H, Zhang J et al. HIV-1 Tat protein increases microglial outward K(+) current and resultant neurotoxic activity. PLoS One 2013; 8:e64904 [View Article][PubMed]
     [Google Scholar]
  36. Bubien JK, Benveniste EN, Benos DJ. HIV-gp120 activates large-conductance apamin-sensitive potassium channels in rat astrocytes. Am J Physiol 1995; 268:C1440–1449[PubMed] [Crossref]
     [Google Scholar]
  37. Brouillette J, Grandy SA, Jolicoeur P, Fiset C. Cardiac repolarization is prolonged in CD4C/HIV transgenic mice. J Mol Cell Cardiol 2007; 43:159–167 [View Article][PubMed]
     [Google Scholar]
  38. Bai YL, Liu HB, Sun B, Zhang Y, Li Q et al. HIV Tat protein inhibits hERG K+ channels: a potential mechanism of HIV infection induced LQTs. J Mol Cell Cardiol 2011; 51:876–880 [View Article][PubMed]
     [Google Scholar]
  39. Karnik R, Ludlow MJ, Abuarab N, Smith AJ, Hardy ME et al. Endocytosis of HERG is clathrin-independent and involves arf6. PLoS One 2013; 8:e85630 [View Article][PubMed]
     [Google Scholar]
  40. Steinke K, Sachse F, Ettischer N, Strutz-Seebohm N, Henrion U et al. Coxsackievirus B3 modulates cardiac ion channels. FASEB J 2013; 27:4108–4121 [View Article][PubMed]
     [Google Scholar]
  41. Su Y-G, Yang Y-Z, Bao W-S, Liu G‐X, Ge JB et al. Effects of taurine and Astragalus membranaceus on ion currents and their expression in cardiomyocytes after CVB3 infection. Drug Dev Res 2003; 58:57–60 [Crossref]
     [Google Scholar]
  42. Kunzelmann K, Sun J, Meanger J, King NJ, Cook DI. Inhibition of airway Na+ transport by respiratory syncytial virus. J Virol 2007; 81:3714–3720 [View Article][PubMed]
     [Google Scholar]
  43. Hoffmann HH, Palese P, Shaw ML. Modulation of influenza virus replication by alteration of sodium ion transport and protein kinase C activity. Antiviral Res 2008; 80:124–134 [View Article][PubMed]
     [Google Scholar]
  44. Kunzelmann K, Beesley AH, King NJ, Karupiah G, Young JA et al. Influenza virus inhibits amiloride-sensitive Na+ channels in respiratory epithelia. Proc Natl Acad Sci USA 2000; 97:10282–10287 [View Article][PubMed]
     [Google Scholar]
  45. Lewis SA. Influenza influences ion channels. J Physiol 2009; 587:3055 [View Article][PubMed]
     [Google Scholar]
  46. Lazrak A, Iles KE, Liu G, Noah DL, Noah JW et al. Influenza virus M2 protein inhibits epithelial sodium channels by increasing reactive oxygen species. FASEB J 2009; 23:3829–3842 [View Article][PubMed]
     [Google Scholar]
  47. Londino JD, Lazrak A, Jurkuvenaite A, Collawn JF, Noah JW et al. Influenza matrix protein 2 alters CFTR expression and function through its ion channel activity. Am J Physiol Lung Cell Mol Physiol 2013; 304:L582–L592 [View Article][PubMed]
     [Google Scholar]
  48. Reddy MM, Light MJ, Quinton PM. Activation of the epithelial Na+ channel (ENaC) requires CFTR Cl- channel function. Nature 1999; 402:301–304 [View Article][PubMed]
     [Google Scholar]
  49. Gallacher M, Brown SG, Hale BG, Fearns R, Olver RE et al. Cation currents in human airway epithelial cells induced by infection with influenza A virus. J Physiol 2009; 587:3159–3173 [View Article][PubMed]
     [Google Scholar]
  50. Ji HL, Song W, Gao Z, Su XF, Nie HG et al. SARS-CoV proteins decrease levels and activity of human ENaC via activation of distinct PKC isoforms. Am J Physiol Lung Cell Mol Physiol 2009; 296:L372–383 [View Article][PubMed]
     [Google Scholar]
  51. Song W, Liu G, Bosworth CA, Walker JR, Megaw GA et al. Respiratory syncytial virus inhibits lung epithelial Na+ channels by up-regulating inducible nitric-oxide synthase. J Biol Chem 2009; 284:7294–7306 [View Article][PubMed]
     [Google Scholar]
  52. Segovia J, Sabbah A, Mgbemena V, Tsai SY, Chang TH et al. TLR2/MyD88/NF-κB pathway, reactive oxygen species, potassium efflux activates NLRP3/ASC inflammasome during respiratory syncytial virus infection. PLoS One 2012; 7:e29695 [View Article][PubMed]
     [Google Scholar]
  53. Ichinohe T, Pang IK, Iwasaki A. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat Immunol 2010; 11:404–410 [View Article][PubMed]
     [Google Scholar]
  54. Nieto-Torres JL, Verdiá-Báguena C, Castaño-Rodriguez C, Aguilella VM, Enjuanes L. Relevance of viroporin ion channel activity on viral replication and pathogenesis. Viruses 2015; 7:3552–3573 [View Article][PubMed]
     [Google Scholar]
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Viral dependence on cellular ion channels – an emerging anti-viral target?
J. Gen. Virol. 98, 345 (2017); https://doi.org/10.1099/jgv.0.000712
/content/journal/jgv/10.1099/jgv.0.000712
/content/journal/jgv/10.1099/jgv.0.000712
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