Ion channels as antivirus targets

Abstract

Ion channels are membrane proteins that are found in a number of viruses and which are of crucial physiological importance in the viral life cycle. They have one common feature in that their action mode involves a change of electrochemical or proton gradient across the bilayer lipid membrane which modulates viral or cellular activity. We will discuss a group of viral channel proteins that belong to the viroproin family, and which participate in a number of viral functions including promoting the release of viral particles from cells. Blocking these channel-forming proteins may be “lethal”, which can be a suitable and potential therapeutic strategy. In this review we discuss seven ion channels of viruses which can lead serious infections in human beings: M2 of influenza A, NB and BM2 of influenza B, CM2 of influenza C, Vpu of HIV-1, p7 of HCV and 2B of picornaviruses.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Agirre A, Barco A, Carrasco L, et al. 2002. Viroporin-mediated membrane permeabilization. Pore formation by nonstructural poliovirus 2B protein. J Biol Chem, 277: 40034–40441.

    Article  CAS  Google Scholar 

  2. 2.

    Becker C F W, Oblatt-Montal M, Kochendoerfer G G, et al. 2004. Chemical synthesis and single channel properties of tetrameric and pentameric TASPs (template-assembled synthetic proteins) derived from the trans-membrane domain of HIV virus protein u (Vpu). J Biol Chem, 279: 17483–17489.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Benjamin J, Chen G P L, David Jackson, Robert A Lamb. 2008. The Influenza virus M2 protein cytoplasmic tail interacts with the M1 protein and influences virus assembly at the site of virus budding. J Virol, 82: 10059–10070.

    Article  CAS  Google Scholar 

  4. 4.

    Betakova T, Hay A J. 2007. Evidence that the CM2 protein of influenza C virus can modify the pH of the exocytic pathway of transfected cells. J Gen Virol, 88: 2291–2296.

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Bour S S U, Strebel K. 1995. The Human immunodeficiency virus type 1 Vpu protein specifically binds to the cytoplasmic domain of CD4-implications for the mechanism degradation. J Virol, 69: 1510–1520.

    PubMed  CAS  Google Scholar 

  6. 6.

    Cady S. D, Hong M. 2008. AAmantadine-induced conformational and dynamical changes of the influenza M2 transmembrane proton channel. Proc Natl Acad Sci USA, 105: 1483–1488.

    PubMed  Article  Google Scholar 

  7. 7.

    Carrasco L G R, Irurzun A, Barco A. 2002. Effects of viral replication on cellular membrane metabolism and function. Mol Biol Picorna Virus: 337–354.

  8. 8.

    Carrere-Kremer S, Montpellier-Pala C, Cocquerel L, et al. 2002. Subcellular localization and topology of the p7 polypeptide of hepatitis C virus. J Virol, 76: 3720–3730.

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Chen H, Wu Y, Voth G A. 2007. Proton transport behavior through the influenza A M2 channel: insights from molecular simulation. Biophys J, 93: 3470–3479.

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Clarke D, Griffin S, Beales L, et al. 2006. Evidence for the formation of a heptameric ion channel complex by the hepatitis C virus p7 protein in vitro. J Biolog Chem, 281: 37057–37068.

    Article  CAS  Google Scholar 

  11. 11.

    Cohen E A, Terwilliger E F, Sodroski J G, et al. 1988. Identification of a protein encoded by the Vpu gene of HIV-1. Nature, 334: 532–534.

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Cross T A. 2009. Flu BM2 structure and function. Nat Struc Mol Biol, 16: 1207–1209.

    Article  CAS  Google Scholar 

  13. 13.

    Davies W L, Hoffmann C E, Paulshock M, et al. 1964. Antiviral activity of 1- adamantanamine (amantadine). Science, 144: 862–863.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    De Jong A S, Wessels E, Dijkman H B, et al. 2003. Determinants for membrane association and permeabilization of the coxsackievirus 2B protein and the identification of the Golgi complex as the target organelle. J Biol Chem, 278: 1012–1021.

    PubMed  Article  Google Scholar 

  15. 15.

    De Jong A S, Melchers W J, Glaudemans D H, et al. 2004. Mutational analysis of different regions in the coxsackievirus 2B protein: Requirements for homomultimerization, membrane permeabilization, subcellular localization, and virus replication. J Biol Chem, 279: 19924–19935.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Deltenre P, Henrion J, Canva V, et al. 2004. Evaluation of amantadine in chronic hepatitis C: a meta-analysis. J Hepatol, 41: 462–473.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Feld J J, Hoofnagle J H. 2005. Mechanism of action of interferon and ribavirin in treatment of hepatitis C. Nature (London), 436: 967–972.

    Article  CAS  Google Scholar 

  18. 18.

    Fischer W. 2005. Viral Memberane Proteins: Structure, Function and Drug Design. Chapter 15. New York: Kluwer Academic/Plenum Publisher.

    Google Scholar 

  19. 19.

    Fischer W B, Pitkeathly M, Sansom M S P. 2001. Amantadine blocks channel activity of the transmembrane segment of the NB protein from influenza B. Eur Biophys J Biophy Letters, 30: 416–420.

    Article  CAS  Google Scholar 

  20. 20.

    Fisher W B, Kruger gens. 2009. Viral channel-forming proteins. Inter Rev Cell Mol Biol, 275: 35–63.

    Article  CAS  Google Scholar 

  21. 21.

    Fischer W B, Sansom M S P. 2002. Viral ion channels: structure and function. Biochim Biophys Acta, 1561: 27–45.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Forrest L R, Kukol A, Arkin I T, et al. 2000. Exploring models of the influenza A M2 channel: MD simulations in a phospholipid bilayer. Biophys J, 78: 55–69.

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Forrest L R, DeGrado W F, Dieckmann G R, et al. 1998. Two models of the influenza A M2 channel domain: verification by comparison. Fold Des, 3: 443–448.

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Gage W P, Gary E, et al. 2005. Virus Ion Channels Formed by Vpu of HIV-1, the 6K Protein of Alphaviruses and NB of Influenza B Virus. In: Viral Membrane Proteins: Structure, Function, and Drug Design (Fischer W B, Ewart G, Melton J, et al. eds.), New York: Kluwer Academic/Plenum Publishers. p207–231.

    Google Scholar 

  25. 25.

    Giffin K, Rader R K, Marino M H, et al. 1995. Novel assay for the influenza virus M2 channel activity. FEBS Lett, 357: 269–274.

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Gonzalez M E, Carrasco L. 2003. Viroporins. FEBS Lett, 552: 28–34.

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Grambas S, Bennett M S, Hay A J. 1992. Influence of amantadine resistance mutations on the pH regulatory function of the M2 protein of influenza A viruses. Virology, 191: 541–549.

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Grantham M L, Wu W H, Lalime E N, et al. 2009. Palmitoylation of the influenza A virus M2 protein is not required for virus replication in vitro but contributes to virus virulence. J Virol, 83: 8655–8661.

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Griffin S, Clarke D, McCormick C, et al. 2005. Signal peptide cleavage and internal targeting signals direct the hepatitis C virus p7 protein to distinct intracellular membranes. J Virol, 79: 15525–15536.

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Griffin S, StGelais C, Owsianka A M, et al. 2008. Genotype-dependent sensitivity of hepatitis C virus to inhibitors of the p7 ion channel. Hepatology, 48: 1779–1790.

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Griffin S D C, Beales L P, Clarke D S, et al. 2003. The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine. FEBS Lett, 535: 34–38.

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Griffin S D C, Harvey R, Clarke D S, et al. 2004. A conserved basic loop in hepatitis C virus p7 protein is required for amantadine-sensitive ion channel activity in mammalian cells but is dispensable for localization to mitochondria. J Gen Virol, 85: 451–461.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Gupta R K, Towers G J. 2009. A tail of tetherin: how pandemic HIV-1 conquered the world. Cell Host Microbe, 6: 393–395.

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Hamman J H, Enslin G M, Kotze A F. 2005. Oral delivery of peptide drugs: barriers and developments. Biodrugs, 19: 165–177.

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Harada T, Tautz N, Thiel H-J. 2000. E2-p7 region of the bovine viral diarrhea virus polyprotein: processing and functional studies. J Virol, 74: 9498–9506.

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Hay A J. 1992. The action of adamantanamines against influenza A viruses: Inhibition of the M2 ion channel protein. Sem Virol, 3: 21–30.

    CAS  Google Scholar 

  37. 37.

    Henklein P, Kinder R, Schubert U, et al. 2000. Membrane interactions and alignment of structures within the HIV-1 Vpu cytoplasmic domain: effect of phosphorylation of serines 52 and 56. FEBS Lett, 482: 220–224.

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Holsinger L J, Lamb R A. 1991. Influenza virus M2 integral membrane-protein is homotetramer stabilized by formation of disulfide bonds. Virology, 183: 32–43.

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Holsinger L J, Shaughnessy M A, Micko A, et al. 1995. Analysis of the posttranslational modifications of the influenza-virus M2 protein. J Virol, 69: 1219–1225.

    PubMed  CAS  Google Scholar 

  40. 40.

    Hongo S, Ishii K, Mori K, et al. 2004. Detection of ion channel activity in xenopus iaevis oocytes expressing influenza C virus CM2 protein. Arch Virol, 149: 35–50.

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Hu J, Fu R, Cross T A. 2007. The chemical and dynamical influence of the anti-viral drug amantadine on the M2 proton channel transmembrane domain. Biophys J, 93: 276–283.

    PubMed  Article  CAS  Google Scholar 

  42. 42.

    Intharathep P, Laohpongspaisan C, Rungrotmongkol T, et al. 2008. How amantadine and rimantadine inhibit proton transport in the M2 protein channel. J Mol Graph Model, 27: 342–348.

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Isherwood B J, Patel A H. 2005. Analysis of the processing and transmembrane topology of the E2p7 protein of hepatitis C virus. J Gen Virol, 86: 667–676.

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Jing X, Ma C, Ohigashi Y, et al. 2008. Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel. Proc Natl Acad Sci USA, 105: 10967–10972.

    PubMed  Article  Google Scholar 

  45. 45.

    Kass I, Arkin I T. 2005. How pH opens a H+ channel: the gating mechanism of influenza a M2. Structure, 13: 1789–1798.

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Klimkait T, Strebel K, Hoggan M D, et al. 1990. The human immunodeficiency virus type 1-specific protein Vpu is required for efficient virus maturation and release. J Virol, 64: 621–629.

    PubMed  CAS  Google Scholar 

  47. 47.

    Kolocouris A, Zikos C, Broadhurst R W. 2007. 19F NMR detection of the complex between amantadine and the receptor portion of the influenza A M2 ion channel in DPC micelles. Bioorg Med Chem Lett, 17: 3947–3952.

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Kukol A, Arkin I T. 2000. Structure of the influenza C virus CM2 protein transmembrane domain obtained by site-specific infrared dichroism and global molecular dynamics searching. J Biolog Chem, 275: 4225–4229.

    Article  CAS  Google Scholar 

  49. 49.

    Lamb R A, Krug R M. 2001. Orthomyxoviridae: The viruses and their replication. In: Fundamental Virology (Knipe D M, Howley P M. eds.), Philadelphia, USA. 605–647.

  50. 50.

    Lamb R A, Zebedee S L, Richardson C D. 1985. Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface. Cell, 40: 627–633.

    PubMed  Article  CAS  Google Scholar 

  51. 51.

    Lemaitre V, Willbold D, Watts A, et al. 2006. Full length Vpu from HIV-1: combining molecular dynamics simulations with NMR spectroscopy. J Biomol Struc Dynamics, 23: 485–496.

    CAS  Google Scholar 

  52. 52.

    Marassi F M, Ma C, Gratkowski H, et al. 1999. Correlation of the structural and functional domains in the membrane protein Vpu from HIV-1. Proc Natl Acad Sci USA, 96: 14336–14341.

    PubMed  Article  CAS  Google Scholar 

  53. 53.

    Merkle I, Van Ooij M J M, Van Kuppeveld F J, et al. 2002. Biological significance of a human enterovirus B-specific RNA element in the 3′ nontranslated region J Virol, 76: 9900–9909.

    PubMed  Article  CAS  Google Scholar 

  54. 54.

    Montal M. 2009. Vpu matchmakers as a therapeutic strategy for HIV infection. PLoS Pathogens, 5: 1–3.

    Article  CAS  Google Scholar 

  55. 55.

    Ma C, Marassi F M, et al. 2002. Expression, purification, and activities of full-length and truncated versions of the integral membrane protein Vpu from HIV-1. Protein Sci, 11: 546–557.

    PubMed  Article  CAS  Google Scholar 

  56. 56.

    Mould J A, Drury J E, Frings S M, et al. 2000. Permeation and activation of the M2 ion channel of influenza A virus. J Biol Chem, 275: 31038–31050.

    PubMed  Article  CAS  Google Scholar 

  57. 57.

    Mould J A, Paterson R G, Takeda M, et al. 2003. Influenza B virus BM2 protein has ion channel activity that conducts protons across membranes. Develop Cell, 5: 175–184.

    Article  CAS  Google Scholar 

  58. 58.

    Neil S J D, Zang T, Bieniasz P D. 2008. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature, 451: 425–U421.

    PubMed  Article  CAS  Google Scholar 

  59. 59.

    Nieva J L, Agirre A, Nir S, et al. 2003. Mechanisms of membrane permeabilization by picornavirus 2B viroporin. FEBS Lett, 552: 68–73.

    PubMed  Article  CAS  Google Scholar 

  60. 60.

    Panayotov P P, Schlesinger R W. 1992. Oligomeric organization and strain-specific protelytic modification of the virion-M2 protein of influenza-A-HINI viruses. Virology, 186: 352–355.

    PubMed  Article  CAS  Google Scholar 

  61. 61.

    Park S H, Mrse A A, Nevzorov A A, et al. 2003. Three-dimensional structure of the channel-forming trans-membrane domain of virus protein “u” (Vpu) from HIV-1. J Mol Biol, 333: 409–424.

    PubMed  Article  CAS  Google Scholar 

  62. 62.

    Patargias G, Zitzmann N, Dwek R, et al. 2006. Protein-protein interactions: Modeling the hepatitis C virus ion channel p7. J Med Chem, 49: 648–655.

    PubMed  Article  CAS  Google Scholar 

  63. 63.

    Pavlovic D, Fischer W, Hussey M, et al. 2005. Long alkylchain iminosugars bloc the HCV p7 ion chanel.. In: Advances in Experimental Medicine and Biology (Axford J S. ed), Netherlands: Springer.564:3–4.

    Google Scholar 

  64. 64.

    Pavlovic D, Neville D C A, Argaud O, et al. 2003. The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives. Proc Natl Acad Sci USA, 100: 6104–6108.

    PubMed  Article  CAS  Google Scholar 

  65. 65.

    Pawlotsky J M. 2006. Therapy of hepatitis C: from empiricism to eradication. Hepatology, 43: S207–S220.

    PubMed  Article  CAS  Google Scholar 

  66. 66.

    Pekosz A, Lamb R A. 1997. The CM2 protein of influenza C virus is an oligomeric integral membrane glycoprotein structurally analogous to influenza A virus M-2 and influenza B virus NB proteins. Virology, 237: 439–451.

    PubMed  Article  CAS  Google Scholar 

  67. 67.

    Pinto L H, Lamb R A. 1995. Understanding the mechanism of action of the anti-influenza virus drug amantadine. Trends Microbiol, 3: 271–271.

    PubMed  Article  CAS  Google Scholar 

  68. 68.

    Premkumar A, Wilson L, Ewart G D, et al. 2004. Cation-selective ion channels formed by p7 of hepatitis C virus are blocked by hexamethylene amiloride. FEBS Lett, 557: 99–103.

    PubMed  Article  CAS  Google Scholar 

  69. 69.

    Sakai A, St Claire M S, Faulk K, et al. 2003. The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences. Proc Natl Acad Sci USA, 100: 11646–11651.

    PubMed  Article  CAS  Google Scholar 

  70. 70.

    Sakai A, St. Claire M, Faulk K, et al. 2003. The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences. Proc Natl Acad Sci USA, 100: 11646–11651.

    PubMed  Article  CAS  Google Scholar 

  71. 71.

    Sandoval I V, Carrasco L. 1997. Poliovirus infection and expression of the poliovirus protein 2B provoke the disassembly of the Golgi complex, the organelle target for the antipoliovirus drug Ro-090179. J Virolol, 71: 4679–4693.

    CAS  Google Scholar 

  72. 72.

    Sansom M S P, Kerr I D, Smith G R, et al. 1997. The influenza A virus M2 channel: a molecular modeling and simulation study. Virology, 233: 163–173.

    PubMed  Article  CAS  Google Scholar 

  73. 73.

    Sarah D Cady, Schmidt-Rohr, Klaus , et al. 2010. Structure of the amantadine binding site of influenza M2 proton channels in lipid bilayers. Nature, 463: 689–692.

    PubMed  Article  CAS  Google Scholar 

  74. 74.

    Sauter D, Schindler M, Specht A, et al. 2009. Tetherin-Driven Adaptation of Vpu and Nef Function and the Evolution of Pandemic and Nonpandemic HIV-1 Strains. Cell Host Microbe, 6: 409–421.

    PubMed  Article  CAS  Google Scholar 

  75. 75.

    Schnell J R, Chou J J. 2008. Structure and mechanism of the M2 proton channel of influenza A virus. Nature, 451: 591–595.

    PubMed  Article  CAS  Google Scholar 

  76. 76.

    Schubert U, Anton L C, Bacik I, et al. 1998. CD4 glycoprotein degradation induced by human immunodeficiency virus type 1 Vpu protein requires the function of proteasomes and the ubiquitin-conjugating pathway. J Virol, 72: 2280–2288.

    PubMed  CAS  Google Scholar 

  77. 77.

    Schubert U, FerrerMontiel A V, OblattMontal M, et al. 1996. Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV-1-infected cells. FEBS Lett, 398: 12–18.

    PubMed  Article  CAS  Google Scholar 

  78. 78.

    Smondyrev A M, Voth G A. 2002. Molecular dynamics simulation of proton transport through the influenza A virus M2 channel. Biophys J, 83: 1987–1996.

    PubMed  Article  CAS  Google Scholar 

  79. 79.

    Steinmann E, Penin F, Kallis S, et al. 2007. Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions. Plos Pathogens, 3: 962–971.

    Article  CAS  Google Scholar 

  80. 80.

    StGelais C, Tuthill T J, Clarke D S, et al. 2007. Inhibition of hepatitis C virus p7 membrane channels in a liposome-based assay system. Antiviral Res, 76: 48–58.

    PubMed  Article  CAS  Google Scholar 

  81. 81.

    Stouffer A L, Ma C, Cristan L, et al. 2008. The interplay of functional tuning, drug resistance, and thermodynamic stability in the evolution of the M2 proton channel from the influenza A virus. Structure, 16: 1067–1076.

    PubMed  Article  CAS  Google Scholar 

  82. 82.

    Strebel K. 2007. HIV accessory genes Vif and Vpu. Adv Pharmacol, 55: 199–232.

    PubMed  Article  CAS  Google Scholar 

  83. 83.

    Stuart J D Neil, Scott W E, Nolwenn Jouvenet, et al. 2006. HIV-1 Vpu promotes release and prevents endocytosis of nascent retrovirus particles from the plasma membrane. PLoS Pathogens, 2: 0354–0367.

    Google Scholar 

  84. 84.

    Sugrue R J, Bahadur G, Zambon M C, et al. 1990. Specific structural alteration of the influenza haemagglutinin by amantadine. EMBO J, 9: 3469–3476.

    PubMed  CAS  Google Scholar 

  85. 85.

    Sugrue R J, Belshe R B, Hay A J. 1990. Palmitoylation of the influenza-A virus M2 protein. Virology, 179: 51–56.

    PubMed  Article  CAS  Google Scholar 

  86. 86.

    Sugrue R J, Hay A J. 1991. Structural characteristics of the M2 protein of influenza-A viruses evidence that it forms a tetrameric channel. Virology, 180: 617–624.

    PubMed  Article  CAS  Google Scholar 

  87. 87.

    Sunstrom N A, Premkumar L S, Premkumar A, et al. 1996. Ion channels formed by NB, an influenza B virus protein. J Membr Biol, 150: 127–132.

    PubMed  Article  CAS  Google Scholar 

  88. 88.

    Taskemasa Sakaguchi Q T, Pinto H Lawrence, Lamb A Robert. 1997. The active oligomeric state of the minimalistic influenza virus M2 ion channel is a tetramer. Proc Natl Acad Sci USA, Vol. 94,.

  89. 89.

    Terwilliger E F, Cohen E A, Lu Y C, et al. 1989. Functional-role of human immunodeficiency virus type-1 Vpu. Proc Nat Acad Sci USA, 86: 5163–5167.

    PubMed  Article  CAS  Google Scholar 

  90. 90.

    Tokarev A, Skasko M, Fitzpatrick K, et al. 2009. Antiviral activity of the interferon-induced cellular protein BST-2/tetherin. Aids Res Human Retroviruses, 25: 1197–1210.

    Article  CAS  Google Scholar 

  91. 91.

    Van Damme N, Goff D, Katsura C, et al. 2008. The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microb, 3: 245–252.

    Article  CAS  Google Scholar 

  92. 92.

    Van Kuppeveld F J, Galama J M, Zoll J, et al. 1996. Coxsackie B3 virus protein 2B contains cationic amphipathic helix that is required for viral RNA replication. J Virol, 70: 3876–3886.

    PubMed  Google Scholar 

  93. 93.

    Van Kuppeveld F J, Hoenderop J G, Smeets R L, et al. 1997. Coxsackievirus protein 2B modifies endoplasmic reticulum membrane and plasma membrane permeability and facilitates virus release. EMBO J, 16: 3519–3532.

    PubMed  Article  Google Scholar 

  94. 94.

    Van Kuppeveld F J, Melchers W J, Kirkegaard K, et al. 1997. Structure-function analysis of coxsackie B3 virus protein 2B. Virology, 227: 111–118.

    Article  Google Scholar 

  95. 95.

    Varthakavi V, Smith R M, Bour S P, et al. 2003. Viral protein U counteracts a human host cell restriction that inhibits HIV-1 particle production. Proc Nat Acad Sci USA, 100: 15154–15159.

    PubMed  Article  CAS  Google Scholar 

  96. 96.

    Veit M, Klenk H D, Kendal A, et al. 1991. The M2 protein of influenza-A virus is acylated. J Gen Virol, 72: 1461–1465.

    PubMed  Article  CAS  Google Scholar 

  97. 97.

    Wang C, Lamb R A, Pinto L H. 1995. Activation of the M2 ion channel of influenza virus- a role for the transmembrane domain histidine residue. Biophys J, 69: 1363–1371.

    PubMed  Article  CAS  Google Scholar 

  98. 98.

    Wang C, Lamb R A, Pinto L H. 1995. Activation of the M2 ion channel of influenza virus: A role for the transmembrane domain histidine residue. Biophys J, 69: 1363–1371.

    PubMed  Article  CAS  Google Scholar 

  99. 99.

    Willbold D, Haider S, Volkmann A, et al. 1995. Structure of the HIV-1 Vpu protein cytoplasmatic domain in aqueous solution. Biolog Chem Hoppe-Seyler, 376: S168.

    Google Scholar 

  100. 100.

    Willbold D, Hoffmann S, Rosch P. 1997. Secondary structure and tertiary fold of the human immunodeficiency virus protein U (Vpu) cytoplasmic domain in solution. Eur J Biochem, 245: 581–588.

    PubMed  Article  CAS  Google Scholar 

  101. 101.

    Willey R L, Maldarelli F, Martin M A, et al. 1992. Human-immunodeficiency-virus type-1 Vpu protein regulates the formation of intracellular GP 160-CD4 complexes. J Virol, 66: 226–234.

    PubMed  CAS  Google Scholar 

  102. 102.

    Woolley G A, Wallace B A. 1992. Model ion channels: gramicidin and alamethicin. J Membrane Biol, 129: 109–136.

    CAS  Google Scholar 

  103. 103.

    Wray V, Schubert U. 2005. Structure, phosphorylation, and biological function of the HIV-1 specific virus protein U (Vpu). Viral Membrane Proteins: Structure, Function, and Drug Design, 1: 165–175.

    Article  CAS  Google Scholar 

  104. 104.

    Yuki Ohigashia Mac, Jing X, et al. 2009. An amantadine -sensitive chimeric BM2 ion channel of influenza B virus has implications for the mechanism of drug inhibition. PNAS, 106: 18775–18779.

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Zhi-yuan Li.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Liang, X., Li, Zy. Ion channels as antivirus targets. Virol. Sin. 25, 267–280 (2010). https://doi.org/10.1007/s12250-010-3136-y

Download citation

Key words

  • Viral ion channel
  • Antiviral therapy
  • Viruses
  • Amantadine