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Targeting host cofactors to inhibit viral infection

Abstract

The majority of FDA-approved drugs indicated for the treatment of viral infections are inhibitors of viral proteins, of which the emergence of resistant strains is a major concern. This issue is exacerbated as most developed antiviral therapies are indicated for the treatment of viruses with error-prone replication. These problems may be addressed by the development of drugs that modulate the function of host factors involved in various aspects of a viral life cycle. Targeting host factors uncouples the mutation of a druggable protein gene from the replication and survival selection pressure exerted on a virus. Currently, a host-targeting antiviral (HTA), maraviroc, is approved for the treatment of human immunodeficiency virus (HIV) infection. In addition, several HTAs indicated for the treatment of hepatitis C virus (HCV) or HIV infection are at various stages of clinical evaluation. Targeting host factors is an attractive complement to therapies directly targeting a viral protein because of the expected higher genetic barrier for resistance and an overall increase in the diversity of treatment options. We examine how the integrated roles of emerging host cofactor screening approaches and drug development strategies may advance current treatment options.

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References

  • Abe K, Ikeda M, Ariumi Y, Dansako H, Wakita T, Kato N (2009). HCV genotype 1b chimeric replicon with NS5B of JFH-1 exhibited resistance to cyclosporine A. Arch Virol, 154(10): 1671–1677

    PubMed  CAS  Google Scholar 

  • Alkhatib G, Combadiere C, Broder C C, Feng Y, Kennedy P E, Murphy P M, Berger E A (1996). CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science, 272(5270): 1955–1958

    PubMed  CAS  Google Scholar 

  • Amara A, Gall S L, Schwartz O, Salamero J, Montes M, Loetscher P, Baggiolini M, Virelizier J L, Arenzana-Seisdedos F (1997). HIV coreceptor downregulation as antiviral principle: SDF-1alphadependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication. J Exp Med, 186(1): 139–146

    PubMed  CAS  Google Scholar 

  • Arnett S O, Teillaud J L, Wurch T, Reichert J M, Dunlop C, Huber M (2011). IBC’s 21st Annual Antibody Engineering and 8th Annual Antibody Therapeutics International Conferences and 2010 Annual Meeting of the Antibody Society. December 5–9, 2010, San Diego, CA USA. MAbs, 3(2): 133–152

    Google Scholar 

  • Bai S, Nasser M W, Wang B, Hsu S H, Datta J, Kutay H, Yadav A, Nuovo G, Kumar P, Ghoshal K (2009). MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem, 284(46): 32015–32027

    PubMed  CAS  Google Scholar 

  • Bartosch B, Vitelli A, Granier C, Goujon C, Dubuisson J, Pascale S, Scarselli E, Cortese R, Nicosia A, Cosset F L (2003). Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor. J Biol Chem, 278(43): 41624–41630

    PubMed  CAS  Google Scholar 

  • Berson J F, Long D, Doranz B J, Rucker J, Jirik F R, Doms R W (1996). A seven-transmembrane domain receptor involved in fusion and entry of T-cell-tropic human immunodeficiency virus type 1 strains. J Virol, 70(9): 6288–6295

    PubMed  CAS  Google Scholar 

  • Bleul C C, Farzan M, Choe H, Parolin C, Clark-Lewis I, Sodroski J, Springer T A (1996). The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature, 382(6594): 829–833

    PubMed  CAS  Google Scholar 

  • Borner K, Hermle J, Sommer C, Brown N P, Knapp B, Glass B, Kunkel J, Torralba G, Reymann J, Beil N, Beneke J, Pepperkok R, Schneider R, Ludwig T, Hausmann M, Hamprecht F, Erfle H, Kaderali L, Kräusslich H G, Lehmann M J (2010). From experimental setup to bioinformatics: an RNAi screening platform to identify host factors involved in HIV-1 replication. Biotechnol J, 5(1): 39–49

    PubMed  Google Scholar 

  • Brass A L, Dykxhoorn D M, Benita Y, Yan N, Engelman A, Xavier R J, Lieberman J, Elledge S J (2008). Identification of host proteins required for HIV infection through a functional genomic screen. Science, 319(5865): 921–926

    PubMed  CAS  Google Scholar 

  • Bright R A, Shay D K, Shu B, Cox N J, Klimov A I (2006). Adamantane resistance among influenza A viruses isolated early during the 2005–2006 influenza season in the United States. JAMA, 295(8): 891–894

    PubMed  CAS  Google Scholar 

  • Brimacombe C L, Grove J, Meredith LW, Hu K, Syder A J, Flores MV, Timpe JM, Krieger S E, Baumert T F, Tellinghuisen T L, Wong-Staal F, Balfe P, McKeating J A (2011). Neutralizing antibody-resistant hepatitis C virus cell-to-cell transmission. J Virol, 85(1): 596–605

    PubMed  CAS  Google Scholar 

  • Brumme Z L, Goodrich J, Mayer H B, Brumme C J, Henrick B M, Wynhoven B, Asselin J J, Cheung P K, Hogg R S, Montaner J S G, Harrigan P R (2005). Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals. J Infect Dis, 192(3): 466–474

    PubMed  CAS  Google Scholar 

  • Bruno C J, Jacobson J M (2010). Ibalizumab: an anti-CD4 monoclonal antibody for the treatment of HIV-1 infection. J Antimicrob Chemother, 65(9): 1839–1841

    PubMed  CAS  Google Scholar 

  • Bushman F D, Malani N, Fernandes J, D’Orso I, Cagney G, Diamond T L, Zhou H, Hazuda D J, Espeseth A S, König R, Bandyopadhyay S, Ideker T, Goff S P, Krogan N J, Frankel A D, Young J A, Chanda S K (2009). Host cell factors in HIV replication: meta-analysis of genome-wide studies. PLoS Pathog, 5(5): e1000437

    PubMed  Google Scholar 

  • Calderwood M A, Venkatesan K, Xing L, Chase M R, Vazquez A, Holthaus A M, Ewence A E, Li N, Hirozane-Kishikawa T, Hill D E, Vidal M, Kieff E, Johannsen E (2007). Epstein-Barr virus and virus human protein interaction maps. Proc Natl Acad Sci USA, 104(18): 7606–7611

    PubMed  CAS  Google Scholar 

  • Cavalluzzo C, Voet A, Christ F, Singh B K, Sharma A, Debyser Z, Maeyer M D, der Eycken E V (2012). De novo design of small molecule inhibitors targeting the LEDGF/p75-HIV integrase interaction. RSC Advances, 2(3): 974

    CAS  Google Scholar 

  • Chan D C, Kim P S (1998). HIV entry and its inhibition. Cell, 93(5): 681–684

    PubMed  CAS  Google Scholar 

  • Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia M A, Xu C, Mason WS, Moloshok T, Bort R, Zaret K S, Taylor JM (2004). miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol, 1(2): 106–113

    PubMed  CAS  Google Scholar 

  • Charlton K M, Casey G A (1979). Experimental rabies in skunks: immunofluorescence light and electron microscopic studies. Lab Invest, 41(1): 36–44

    PubMed  CAS  Google Scholar 

  • Chatterji U, Bobardt M, Selvarajah S, Yang F, Tang H, Sakamoto N, Vuagniaux G, Parkinson T, Gallay P (2009). The isomerase active site of cyclophilin A is critical for hepatitis C virus replication. J Biol Chem, 284(25): 16998–17005

    PubMed  CAS  Google Scholar 

  • Cherepanov P, Maertens G, Proost P, Devreese B, Van Beeumen J, Engelborghs Y, De Clercq E, Debyser Z (2003). HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells. J Biol Chem, 278(1): 372–381

    PubMed  CAS  Google Scholar 

  • Christ F, Voet A, Marchand A, Nicolet S, Desimmie B A, Marchand D, Bardiot D, Van der Veken N J, Van Remoortel B, Strelkov S V, De Maeyer M, Chaltin P, Debyser Z (2010). Rational design of smallmolecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication. Nat Chem Biol, 6(6): 442–448

    PubMed  CAS  Google Scholar 

  • Ciesek S, Steinmann E, Wedemeyer H, Manns M P, Neyts J, Tautz N, Madan V, Bartenschlager R, von Hahn T, Pietschmann T (2009). Cyclosporine A inhibits hepatitis C virus nonstructural protein 2 through cyclophilin A. Hepatology, 50(5): 1638–1645

    PubMed  CAS  Google Scholar 

  • Cocchi F, DeVico A L, Garzino-Demo A, Arya S K, Gallo R C, Lusso P (1995). Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science, 270(5243): 1811–1815

    PubMed  CAS  Google Scholar 

  • Coffin J M (1995). HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science, 267(5197): 483–489

    PubMed  CAS  Google Scholar 

  • Coulouarn C, Factor V M, Andersen J B, Durkin M E, Thorgeirsson S S (2009). Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene, 28(40): 3526–3536

    PubMed  CAS  Google Scholar 

  • Dalgleish A G, Beverley P C, Clapham P R, Crawford D H, Greaves M F, Weiss R A (1984). The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature, 312(5996): 763–767

    PubMed  CAS  Google Scholar 

  • de Chassey B, Navratil V, Tafforeau L, Hiet M S, Aublin-Gex A, Agaugué S, Meiffren G, Pradezynski F, Faria B F, Chantier T, Le Breton M, Pellet J, Davoust N, Mangeot P E, Chaboud A, Penin F, Jacob Y, Vidalain P O, Vidal M, André P, Rabourdin-Combe C, Lotteau V (2008). Hepatitis C virus infection protein network. Mol Syst Biol, 4: 230

    PubMed  Google Scholar 

  • Deen K C, McDougal J S, Inacker R, Folena-Wasserman G, Arthos J, Rosenberg J, Maddon P J, Axel R, Sweet RW (1988). A soluble form of CD4 (T4) protein inhibits AIDS virus infection. Nature, 331(6151): 82–84

    PubMed  CAS  Google Scholar 

  • Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton R E, Hill C M, Davis C B, Peiper S C, Schall T J, Littman D R, Landau N R (1996). Identification of a major coreceptor for primary isolates of HIV-1. Nature, 381(6584): 661–666

    PubMed  CAS  Google Scholar 

  • Deyde V M, Xu X, Bright R A, Shaw M, Smith C B, Zhang Y, Shu Y, Gubareva L V, Cox N J, Klimov A I (2007). Surveillance of resistance to adamantanes among influenza A(H3N2) and A(H1N1) viruses isolated worldwide. J Infect Dis, 196(2): 249–257

    PubMed  CAS  Google Scholar 

  • Donzella G A, Schols D, Lin SW, Esté J A, Nagashima K A, Maddon P J, Allaway G P, Sakmar T P, Henson G, De Clercq E, Moore J P (1998). AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nat Med, 4(1): 72–77

    PubMed  CAS  Google Scholar 

  • Dragic T, Litwin V, Allaway G P, Martin S R, Huang Y, Nagashima K A, Cayanan C, Maddon P J, Koup R A, Moore J P, Paxton W A (1996). HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature, 381(6584): 667–673

    PubMed  CAS  Google Scholar 

  • Dumond J B, Patterson K B, Pecha A L, Werner R E, Andrews E, Damle B, Tressler R, Worsley J, Kashuba A D M (2009). Maraviroc concentrates in the cervicovaginal fluid and vaginal tissue of HIVnegative women. J Acquir Immune Defic Syndr, 51(5): 546–553

    PubMed  Google Scholar 

  • Emiliani S, Mousnier A, Busschots K, Maroun M, Van Maele B, Tempé D, Vandekerckhove L, Moisant F, Ben-Slama L, Witvrouw M, Christ F, Rain J C, Dargemont C, Debyser Z, Benarous R (2005). Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication. J Biol Chem, 280(27): 25517–25523

    PubMed  CAS  Google Scholar 

  • Evans M J, von Hahn T, Tscherne D M, Syder A J, Panis M, Wölk B, Hatziioannou T, McKeating J A, Bieniasz P D, Rice C M (2007). Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature, 446(7137): 801–805

    PubMed  CAS  Google Scholar 

  • Feng Y, Broder C C, Kennedy P E, Berger E A (1996). HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science, 272(5263): 872–877

    PubMed  CAS  Google Scholar 

  • Flint M, Maidens C, Loomis-Price L D, Shotton C, Dubuisson J, Monk P, Higginbottom A, Levy S, McKeating J A (1999). Characterization of hepatitis C virus E2 glycoprotein interaction with a putative cellular receptor, CD81. J Virol, 73(8): 6235–6244

    PubMed  CAS  Google Scholar 

  • Flisiak R, Feinman S V, Jablkowski M, Horban A, Kryczka W, Pawlowska M, Heathcote J E, Mazzella G, Vandelli C, Nicolas-Métral V, Grosgurin P, Liz J S, Scalfaro P, Porchet H, Crabbé R (2009). The cyclophilin inhibitor Debio 025 combined with PEG IFNα2a significantly reduces viral load in treatment-naïve hepatitis C patients. Hepatology, 49(5): 1460–1468

    PubMed  CAS  Google Scholar 

  • Flisiak R, Horban A, Gallay P, Bobardt M, Selvarajah S, Wiercinska-Drapalo A, Siwak E, Cielniak I, Higersberger J, Kierkus J, Aeschlimann C, Grosgurin P, Nicolas-Métral V, Dumont J M, Porchet H, Crabbé R, Scalfaro P (2008). The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus. Hepatology, 47(3): 817–826

    PubMed  CAS  Google Scholar 

  • Foster T L, Gallay P, Stonehouse N J, Harris M (2011). Cyclophilin A interacts with domain II of hepatitis C virus NS5A and stimulates RNA binding in an isomerase-dependent manner. J Virol, 85(14): 7460–7464

    PubMed  CAS  Google Scholar 

  • Gaertner H, Cerini F, Escola J M, Kuenzi G, Melotti A, Offord R, Rossitto-Borlat I, Nedellec R, Salkowitz J, Gorochov G, Mosier D, Hartley O (2008). Highly potent, fully recombinant anti-HIV chemokines: reengineering a low-cost microbicide. Proc Natl Acad Sci USA, 105(46): 17706–17711

    PubMed  CAS  Google Scholar 

  • Grant R M, Lama J R, Anderson P L, McMahan V, Liu A Y, Vargas L, Goicochea P, Casapía M, Guanira-Carranza J V, Ramirez-Cardich M E, Montoya-Herrera O, Fernández T, Veloso V G, Buchbinder S P, Chariyalertsak S, Schechter M, Bekker L G, Mayer K H, Kallás E G, Amico K R, Mulligan K, Bushman L R, Hance R J, Ganoza C, Defechereux P, Postle B, Wang F, McConnell J J, Zheng J H, Lee J, Rooney J F, Jaffe H S, Martinez A I, Burns D N, Glidden D V, iPrEx Study Team (2010). Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med, 363(27): 2587–2599

    PubMed  CAS  Google Scholar 

  • Gregory M A, Bobardt M, Obeid S, Chatterji U, Coates N J, Foster T, Gallay P, Leyssen P, Moss S J, Neyts J, Nur-e-Alam M, Paeshuyse J, Piraee M, Suthar D, Warneck T, Zhang M Q, Wilkinson B (2011). Preclinical characterization of naturally occurring polyketide cyclophilin inhibitors from the sanglifehrin family. Antimicrob Agents Chemother, 55(5): 1975–1981

    PubMed  CAS  Google Scholar 

  • Groot F, Welsch S, Sattentau Q J (2008). Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses. Blood, 111(9): 4660–4663

    PubMed  CAS  Google Scholar 

  • Grove J, Nielsen S, Zhong J, Bassendine M F, Drummer H E, Balfe P, McKeating J A (2008). Identification of a residue in hepatitis C virus E2 glycoprotein that determines scavenger receptor BI and CD81 receptor dependency and sensitivity to neutralizing antibodies. J Virol, 82(24): 12020–12029

    PubMed  CAS  Google Scholar 

  • Hamamoto I, Nishimura Y, Okamoto T, Aizaki H, Liu M, Mori Y, Abe T, Suzuki T, Lai M M C, Miyamura T, Moriishi K, Matsuura Y (2005). Human VAP-B is involved in hepatitis C virus replication through interaction with NS5A and NS5B. J Virol, 79(21): 13473–13482

    PubMed  CAS  Google Scholar 

  • Hartley O, Gaertner H, Wilken J, Thompson D, Fish R, Ramos A, Pastore C, Dufour B, Cerini F, Melotti A, Heveker N, Picard L, Alizon M, Mosier D, Kent S, Offord R (2004). Medicinal chemistry applied to a synthetic protein: development of highly potent HIV entry inhibitors. Proc Natl Acad Sci USA, 101(47): 16460–16465

    PubMed  CAS  Google Scholar 

  • Hendrix C W, Collier A C, Lederman M M, Schols D, Pollard R B, Brown S, Jackson J B, Coombs R W, Glesby M J, Flexner C W, Bridger G J, Badel K, MacFarland R T, Henson G W, Calandra G, AMD3100 HIV Study Group (2004). Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection. J Acquir Immune Defic Syndr, 37(2): 1253–1262

    PubMed  CAS  Google Scholar 

  • Henke J I, Goergen D, Zheng J, Song Y, Schüttler C G, Fehr C, Jünemann C, Niepmann M (2008). microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J, 27(24): 3300–3310

    PubMed  CAS  Google Scholar 

  • Heo T H (2008). A potential role of the heparan sulfate in the hepatitis C virus attachment. Acta Virol, 52(1): 7–15

    PubMed  CAS  Google Scholar 

  • Hildebrandt-Eriksen E S, Aarup V, Persson R, Hansen H F, Munk M E, Orum H (2012). A locked nucleic acid oligonucleotide targeting microRNA 122 is well-tolerated in cynomolgus monkeys. Nucleic Acid Therapeutics, 22(3): 152–161

    PubMed  CAS  Google Scholar 

  • Ho D D, Neumann A U, Perelson A S, Chen W, Leonard J M, Markowitz M (1995). Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature, 373(6510): 123–126

    PubMed  CAS  Google Scholar 

  • Hopkins S, Dimassimo B, Rusnak P, Heuman D, Lalezari J, Sluder A., Scorneaux B, Mosier S, Kowalczyk P, Ribeill Y, Baugh J, Gallay P (2012). The cyclophilin inhibitor SCY-635 suppresses viral replication and induces endogenous interferons in patients with chronic HCV genotype 1 infection. J Hepatol, doi: 10.1016/j.jhep.2012.02.024

  • Hopkins S, Heuman D, Gavis E, Lalezari J, Glutzer E, DiMassimo B, Rusnak P, Wring S, Smitley C, Ribeill Y (2009). Safety, plasma, pharmacokinetics, and anti-viral activity of SCY-635 in adult patients with chronic hepatitis C virus infection. J Hepatol, 50S: 36

    Google Scholar 

  • Inoue K, Umehara T, Ruegg U T, Yasui F, Watanabe T, Yasuda H, Dumont JM, Scalfaro P, Yoshiba M, Kohara M (2007). Evaluation of a cyclophilin inhibitor in hepatitis C virus-infected chimeric mice in vivo. Hepatology, 45(4): 921–928

    PubMed  CAS  Google Scholar 

  • Iwasaki Y, Clark H F (1975). Cell to cell transmission of virus in the central nervous system. II. Experimental rabies in mouse. Lab Invest, 33(4): 391–399

    PubMed  CAS  Google Scholar 

  • Jacobson J M, Thompson M A, Lalezari J P, Saag M S, Zingman B S, D’Ambrosio P, Stambler N, Rotshteyn Y, Marozsan A J, Maddon P J, Morris S A, Olson W C (2010). Anti-HIV-1 activity of weekly or biweekly treatment with subcutaneous PRO 140, a CCR5 monoclonal antibody. J Infect Dis, 201(10): 1481–1487

    PubMed  CAS  Google Scholar 

  • Jepsen J S, Sørensen M D, Wengel J (2004). Locked nucleic acid: a potent nucleic acid analog in therapeutics and biotechnology. Oligonucleotides, 14(2): 130–146

    PubMed  CAS  Google Scholar 

  • Jolly C, Kashefi K, Hollinshead M, Sattentau Q J (2004). HIV-1 cell to cell transfer across an Env-induced, actin-dependent synapse. J Exp Med, 199(2): 283–293

    PubMed  CAS  Google Scholar 

  • Jopling C L, Schütz S, Sarnow P (2008). Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host Microbe, 4(1): 77–85

    PubMed  CAS  Google Scholar 

  • Jopling C L, Yi M, Lancaster A M, Lemon S M, Sarnow P (2005). Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science, 309(5740): 1577–1581

    PubMed  CAS  Google Scholar 

  • Kaul A, Stauffer S, Berger C, Pertel T, Schmitt J, Kallis S, Zayas M, Lohmann V, Luban J, Bartenschlager R (2009). Essential role of cyclophilin A for hepatitis C virus replication and virus production and possible link to polyprotein cleavage kinetics. PLoS Pathog, 5(8): e1000546

    PubMed  Google Scholar 

  • Klatzmann D, Champagne E, Chamaret S, Gruest J, Guetard D, Hercend T, Gluckman J C, Montagnier L (1984). T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature, 312(5996): 767–768

    PubMed  CAS  Google Scholar 

  • Klibanov O M, Williams S H, Iler C A (2010). Cenicriviroc, an orally active CCR5 antagonist for the potential treatment of HIV infection. Curr Opin Investig Drugs, 11(8): 940–950

    PubMed  CAS  Google Scholar 

  • König R, Stertz S, Zhou Y, Inoue A, Hoffmann H H, Bhattacharyya S, Alamares J G, Tscherne D M, Ortigoza M B, Liang Y, Gao Q, Andrews S E, Bandyopadhyay S, De Jesus P, Tu B P, Pache L, Shih C, Orth A, Bonamy G, Miraglia L, Ideker T, García-Sastre A, Young J A, Palese P, Shaw M L, Chanda S K (2010). Human host factors required for influenza virus replication. Nature, 463(7282): 813–817

    PubMed  Google Scholar 

  • König R, Zhou Y, Elleder D, Diamond T L, Bonamy G M C, Irelan J T, Chiang C Y, Tu B P, De Jesus P D, Lilley C E, Seidel S, Opaluch A M, Caldwell J S, Weitzman M D, Kuhen K L, Bandyopadhyay S, Ideker T, Orth A P, Miraglia L J, Bushman F D, Young J A, Chanda S K (2008). Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell, 135(1): 49–60

    PubMed  Google Scholar 

  • Koshkin A A, Singh S K, Nielsen P, Rajwanshi V K, Kumar R, Meldgaard M, Olsen C E, Wengel J (1998). LNA (Locked Nucleic Acids): Synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition. Tetrahedron, 54(14): 3607–3630

    CAS  Google Scholar 

  • Krieger M (2001). Scavenger receptor class B type I is a multiligand HDL receptor that influences diverse physiologic systems. J Clin Invest, 108(6): 793–797

    PubMed  CAS  Google Scholar 

  • Kuritzkes D, Kar S, Kirkpatrick P (2008). Maraviroc. Nat Rev Drug Discov, 7(1): 15–16

    CAS  Google Scholar 

  • Kutay H, Bai S, Datta J, Motiwala T, Pogribny I, Frankel W, Jacob S T, Ghoshal K (2006). Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem, 99(3): 671–678

    PubMed  CAS  Google Scholar 

  • Kwo P Y, Lawitz E J, McCone J, Schiff E R, Vierling J M, Pound D, Davis M N, Galati J S, Gordon S C, Ravendhran N, Rossaro L, Anderson F H, Jacobson I M, Rubin R, Koury K, Pedicone L D, Brass C A, Chaudhri E, Albrecht J K, SPRINT-1 investigators (2010). Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatmentnaive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet, 376(9742): 705–716

    PubMed  CAS  Google Scholar 

  • Kwong P D, Wyatt R, Robinson J, Sweet R W, Sodroski J, Hendrickson W A (1998). Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature, 393(6686): 648–659

    PubMed  CAS  Google Scholar 

  • Lacek K, Vercauteren K, Grzyb K, Naddeo M, Verhoye L, Słowikowski M P, Fafi-Kremer S, Patel A H, Baumert T F, Folgori A, Leroux-Roels G, Cortese R, Meuleman P, Nicosia A (2012). Novel human SR-BI antibodies prevent infection and dissemination of HCV in vitro and in humanized mice. J Hepatol, doi: 10.1016/j.jhep.2012.02.018

  • Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T (2002). Identification of tissue-specific microRNAs from mouse. Curr Biol, 12(9): 735–739

    PubMed  CAS  Google Scholar 

  • Landrieu I, Hanoulle X, Bonachera F, Hamel A, Sibille N, Yin Y, Wieruszeski J M, Horvath D, Wei Q, Vuagniaux G, Lippens G (2010). Structural basis for the non-immunosuppressive character of the cyclosporin A analogue Debio 025. Biochemistry, 49(22): 4679–4686

    PubMed  CAS  Google Scholar 

  • Lanford R E, Hildebrandt-Eriksen E S, Petri A, Persson R, Lindow M, Munk M E, Kauppinen S, Ørum H (2010). Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science, 327(5962): 198–201

    PubMed  CAS  Google Scholar 

  • Lawitz E, Godofsky E, Rouzier R, Marbury T, Nguyen T, Ke J, Huang M, Praestgaard J, Serra D, Evans T G (2011). Safety, pharmacokinetics, and antiviral activity of the cyclophilin inhibitor NIM811 alone or in combination with pegylated interferon in HCV-infected patients receiving 14 days of therapy. Antiviral Res, 89(3): 238–245

    PubMed  CAS  Google Scholar 

  • Lederman M M, Veazey R S, Offord R, Mosier D E, Dufour J, Mefford M, Piatak M Jr, Lifson J D, Salkowitz J R, Rodriguez B, Blauvelt A, Hartley O (2004). Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5. Science, 306(5695): 485–487

    PubMed  CAS  Google Scholar 

  • Levy S, Todd S C, Maecker H T (1998). CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system. Annu Rev Immunol, 16(1): 89–109

    PubMed  CAS  Google Scholar 

  • Li Q, Brass A L, Ng A, Hu Z, Xavier R J, Liang T J, Elledge S J (2009). A genome-wide genetic screen for host factors required for hepatitis C virus propagation. Proc Natl Acad Sci USA, 106(38): 16410–16415

    PubMed  CAS  Google Scholar 

  • Liu J, Farmer J D Jr, Lane W S, Friedman J, Weissman I, Schreiber S L (1991). Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell, 66(4): 807–815

    PubMed  CAS  Google Scholar 

  • Liu R, Paxton W A, Choe S, Ceradini D, Martin S R, Horuk R, MacDonald M E, Stuhlmann H, Koup R A, Landau N R (1996). Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell, 86(3): 367–377

    PubMed  CAS  Google Scholar 

  • Liu S, Yang W, Shen L, Turner J R, Coyne C B, Wang T (2009). Tight junction proteins claudin-1 and occludin control hepatitis C virus entry and are downregulated during infection to prevent superinfection. J Virol, 83(4): 2011–2014

    PubMed  CAS  Google Scholar 

  • Liu Z, Yang F, Robotham J M, Tang H (2009). Critical role of cyclophilin A and its prolyl-peptidyl isomerase activity in the structure and function of the hepatitis C virus replication complex. J Virol, 83(13): 6554–6565

    PubMed  CAS  Google Scholar 

  • Lohmann V, Körner F, Koch J, Herian U, Theilmann L, Bartenschlager R (1999). Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science, 285(5424): 110–113

    PubMed  CAS  Google Scholar 

  • Lozach P Y, Amara A, Bartosch B, Virelizier J L, Arenzana-Seisdedos F, Cosset F L, Altmeyer R (2004). C-type lectins L-SIGN and DCSIGN capture and transmit infectious hepatitis C virus pseudotype particles. J Biol Chem, 279(31): 32035–32045

    PubMed  CAS  Google Scholar 

  • Lupberger J, Zeisel M B, Xiao F, Thumann C, Fofana I, Zona L, Davis C, Mee C J, Turek M, Gorke S, Royer C, Fischer B, Zahid M N, Lavillette D, Fresquet J, Cosset F L, Rothenberg SM, Pietschmann T, Patel A H, Pessaux P, Doffoël M, Raffelsberger W, Poch O, McKeating J A, Brino L, Baumert T F (2011). EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy. Nat Med, 17(5): 589–595

    PubMed  CAS  Google Scholar 

  • Mack M, Luckow B, Nelson P J, Cihak J, Simmons G, Clapham P R, Signoret N, Marsh M, Stangassinger M, Borlat F, Wells T N, Schlöndorff D, Proudfoot A E (1998). Aminooxypentane-RANTES induces CCR5 internalization but inhibits recycling: a novel inhibitory mechanism of HIV infectivity. J Exp Med, 187(8): 1215–1224

    PubMed  CAS  Google Scholar 

  • Maertens G, Cherepanov P, Pluymers W, Busschots K, De Clercq E, Debyser Z, Engelborghs Y (2003). LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J Biol Chem, 278(35): 33528–33539

    PubMed  CAS  Google Scholar 

  • Masson D, Koseki M, Ishibashi M, Larson C J, Miller S G, King B D, Tall A R (2009). Increased HDL cholesterol and apoA-I in humans and mice treated with a novel SR-BI inhibitor. Arterioscler Thromb Vasc Biol, 29(12): 2054–2060

    PubMed  CAS  Google Scholar 

  • Mathy J E, Ma S, Compton T, Lin K (2008). Combinations of cyclophilin inhibitor NIM811 with hepatitis C virus NS3-4A protease or NS5B polymerase inhibitors enhance antiviral activity and suppress the emergence of resistance. Antimicrob Agents Chemother, 52(9): 3267–3275

    PubMed  CAS  Google Scholar 

  • McDougal J S, Kennedy M S, Sligh J M, Cort S P, Mawle A, Nicholson J K (1986). Binding of HTLV-III/LAV to T4 + T cells by a complex of the 110K viral protein and the T4 molecule. Science, 231(4736): 382–385

    PubMed  CAS  Google Scholar 

  • McHutchison J G, Everson G T, Gordon S C, Jacobson I M, Sulkowski M, Kauffman R, McNair L, Alam J, Muir A J, PROVE1 Study Team (2009). Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med, 360(18): 1827–1838

    PubMed  CAS  Google Scholar 

  • Meuleman P, Hesselgesser J, Paulson M, Vanwolleghem T, Desombere I, Reiser H, Leroux-Roels G (2008). Anti-CD81 antibodies can prevent a hepatitis C virus infection in vivo. Hepatology, 48(6): 1761–1768

    PubMed  CAS  Google Scholar 

  • Molina S, Castet V, Pichard-Garcia L, Wychowski C, Meurs E, Pascussi J M, Sureau C, Fabre J M, Sacunha A, Larrey D, Dubuisson J, Coste J, McKeating J, Maurel P, Fournier-Wirth C (2008). Serum-derived hepatitis C virus infection of primary human hepatocytes is tetraspanin CD81 dependent. J Virol, 82(1): 569–574

    PubMed  CAS  Google Scholar 

  • Moyle G, DeJesus E, Boffito M, Wong R S, Gibney C, Badel K, MacFarland R, Calandra G, Bridger G, Becker S, X4 Antagonist Concept Trial Study Team (2009). Proof of activity with AMD11070, an orally bioavailable inhibitor of CXCR4-tropic HIV type 1. Clin Infect Dis, 48(6): 798–805

    PubMed  CAS  Google Scholar 

  • Moyle G J, Wildfire A, Mandalia S, Mayer H, Goodrich J, Whitcomb J, Gazzard B G (2005). Epidemiology and predictive factors for chemokine receptor use in HIV-1 infection. J Infect Dis, 191(6): 866–872

    PubMed  Google Scholar 

  • Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T (1996). Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature, 382(6592): 635–638

    PubMed  CAS  Google Scholar 

  • Nahmias Y, Casali M, Barbe L, Berthiaume F, Yarmush M L (2006). Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes. Hepatology, 43(2): 257–265

    PubMed  CAS  Google Scholar 

  • Nedellec R, Coetzer M, Lederman M M, Offord R E, Hartley O, Mosier D E (2011). Resistance to the CCR5 inhibitor 5P12-RANTES requires a difficult evolution from CCR5 to CXCR4 coreceptor use. PLoS ONE, 6(7): e22020

    PubMed  CAS  Google Scholar 

  • Nichols W G, Steel H M, Bonny T, Adkison K, Curtis L, Millard J, Kabeya K, Clumeck N (2008). Hepatotoxicity observed in clinical trials of aplaviroc (GW873140). Antimicrob Agents Chemother, 52(3): 858–865

    PubMed  CAS  Google Scholar 

  • Oberlin E, Amara A, Bachelerie F, Bessia C, Virelizier J L, Arenzana-Seisdedos F, Schwartz O, Heard J M, Clark-Lewis I, Legler D F, Loetscher M, Baggiolini M, Moser B (1996). The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by Tcell-line-adapted HIV-1. Nature, 382(6594): 833–835

    PubMed  CAS  Google Scholar 

  • Obika S, Nanbu D, Hari Y, Andoh J, Morio K, Doi T, Imanishi T (1998). Stability and structural features of the duplexes containing nucleoside analogues with a fixed N-type conformation, 2′-O,4′-C-methyleneribonucleosides. Tetrahedron Lett, 39(30): 5401–540

    CAS  Google Scholar 

  • Paeshuyse J, Kaul A, De Clercq E, Rosenwirth B, Dumont J M, Scalfaro P, Bartenschlager R, Neyts J (2006). The non-immunosuppressive cyclosporin DEBIO-025 is a potent inhibitor of hepatitis C virus replication in vitro. Hepatology, 43(4): 761–770

    PubMed  CAS  Google Scholar 

  • Pastore C, Ramos A, Mosier D E (2004). Intrinsic obstacles to human immunodeficiency virus type 1 coreceptor switching. J Virol, 78(14): 7565–7574

    PubMed  CAS  Google Scholar 

  • Pawlotsky J M (2012). Alisporivir plus Ribavirin is highly effective as interferon-free or interferon-add-on regimen in previously untreated HCV-GT2 or GT3 patients: SVR12 results from VITAL-1 Phase 2b study. 47th Annual Meeting of the European Association for the Study of the Liver, Barcelona

  • Pileri P, Uematsu Y, Campagnoli S, Galli G, Falugi F, Petracca R, Weiner A J, Houghton M, Rosa D, Grandi G, Abrignani S (1998). Binding of hepatitis C virus to CD81. Science, 282(5390): 938–941

    PubMed  CAS  Google Scholar 

  • Ploss A, Evans M J, Gaysinskaya V A, Panis M, You H, De Jong Y P, Rice C M (2009). Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature, 457(7231): 882–886

    PubMed  CAS  Google Scholar 

  • Preston B D, Poiesz B J, Loeb L A (1988). Fidelity of HIV-1 reverse transcriptase. Science, 242(4882): 1168–1171

    PubMed  CAS  Google Scholar 

  • Reece P A (2007). Neuraminidase inhibitor resistance in influenza viruses. J Med Virol, 79(10): 1577–1586

    PubMed  CAS  Google Scholar 

  • Reesink H, Janssen H L A, Zeuzem S, Lawitz E, Rodriguez-Torres M, Patel K, Chen A, Davis C, King B, Levin A (2012). Final Results-Randomized, Double-Blind, Placebo-controlled safety, anti-viralpro-of-of-concept study of miravirsen, an oligonucleotide targeting miR-122, in treatment-naïve patients. 47th Annual Meeting of the European Association for the Study of the Liver, Barcelona

  • Reeves PM, Bommarius B, Lebeis S, McNulty S, Christensen J, Swimm A, Chahroudi A, Chavan R, Feinberg M B, Veach D, Bornmann W, Sherman M, Kalman D (2005). Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases. Nat Med, 11(7): 731–739

    PubMed  CAS  Google Scholar 

  • Richman D D, Bozzette S A (1994). The impact of the syncytiuminducing phenotype of human immunodeficiency virus on disease progression. J Infect Dis, 169(5): 968–974

    PubMed  CAS  Google Scholar 

  • Roberts J D, Bebenek K, Kunkel T A (1988). The accuracy of reverse transcriptase from HIV-1. Science, 242(4882): 1171–1173

    PubMed  CAS  Google Scholar 

  • Roche M, Jakobsen M R, Sterjovski J, Ellett A, Posta F, Lee B, Jubb B, Westby M, Lewin S R, Ramsland P A, Churchill M J, Gorry P R (2011). HIV-1 escape from the CCR5 antagonist maraviroc associated with an altered and less-efficient mechanism of gp120-CCR5 engagement that attenuates macrophage tropism. J Virol, 85(9): 4330–4342

    PubMed  CAS  Google Scholar 

  • Sainz B Jr, Barretto N, Martin D N, Hiraga N, Imamura M, Hussain S, Marsh K A, Yu X, Chayama K, Alrefai W A, Uprichard S L (2012). Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nat Med, 18(2): 281–285

    PubMed  CAS  Google Scholar 

  • Samson M, Libert F, Doranz B J, Rucker J, Liesnard C, Farber C M, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth R J, Collman R G, Doms R W, Vassart G, Parmentier M (1996). Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature, 382(6593): 722–725

    PubMed  CAS  Google Scholar 

  • Sarrazin C, Kieffer T L, Bartels D, Hanzelka B, Müh U, Welker M, Wincheringer D, Zhou Y, Chu H M, Lin C, Weegink C, Reesink H, Zeuzem S, Kwong A D (2007). Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology, 132(5): 1767–1777

    PubMed  CAS  Google Scholar 

  • Saunier B, Triyatni M, Ulianich L, Maruvada P, Yen P, Kohn L D (2003). Role of the asialoglycoprotein receptor in binding and entry of hepatitis C virus structural proteins in cultured human hepatocytes. J Virol, 77(1): 546–559

    PubMed  CAS  Google Scholar 

  • Scarselli E, Ansuini H, Cerino R, Roccasecca RM, Acali S, Filocamo G, Traboni C, Nicosia A, Cortese R, Vitelli A (2002). The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J, 21(19): 5017–5025

    PubMed  CAS  Google Scholar 

  • Shapira S D, Gat-Viks I, Shum B O V, Dricot A, De Grace M M, Wu L, Gupta P B, Hao T, Silver S J, Root D E, Hill D E, Regev A, Hacohen N (2009). A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection. Cell, 139(7): 1255–1267

    PubMed  Google Scholar 

  • Shimakami T, Yamane D, Jangra R K, Kempf B J, Spaniel C, Barton D J, Lemon S M (2012a). Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. Proc Natl Acad Sci USA, 109(3): 941–946

    PubMed  CAS  Google Scholar 

  • Shimakami T, Yamane D, Welsch C, Hensley L, Jangra R K, Lemon S M. (2012b). Base-pairing between Hepatitis C Virus RNA and miR-122 3′ of its Seed Sequence is Essential for Genome Stabilization and Production of Infectious Virus. J Virol

  • Simmons G, Clapham P R, Picard L, Offord R E, Rosenkilde M M, Schwartz T W, Buser R, Wells T N, Proudfoot A E (1997). Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist. Science, 276(5310): 276–279

    PubMed  CAS  Google Scholar 

  • Singh K, Koshkin A A, Wengel J, Nielsen P (1998). LNA (locked nucleic acids): synthesis and high-affinity nucleic acid recognition. Chem Commun (Camb), (4): 455–456

    Google Scholar 

  • Smith D H, Byrn R A, Marsters S A, Gregory T, Groopman J E, Capon D J (1987). Blocking of HIV-1 infectivity by a soluble, secreted form of the CD4 antigen. Science, 238(4834): 1704–1707

    PubMed  CAS  Google Scholar 

  • Song R, Franco D, Kao C Y, Yu F, Huang Y, Ho D D (2010). Epitope mapping of ibalizumab, a humanized anti-CD4 monoclonal antibody with anti-HIV-1 activity in infected patients. J Virol, 84(14): 6935–6942

    PubMed  CAS  Google Scholar 

  • Syder A J, Lee H, Zeisel MB, Grove J, Soulier E, Macdonald J, Chow S, Chang J, Baumert T F, McKeating J A, McKelvy J, Wong-Staal F (2011). Small molecule scavenger receptor BI antagonists are potent HCV entry inhibitors. J Hepatol, 54(1): 48–55

    PubMed  CAS  Google Scholar 

  • Tang H (2010). Cyclophilin inhibitors as a novel HCV therapy. Viruses, 2(8): 1621–1634

    PubMed  CAS  Google Scholar 

  • Teraoka S, Mishiro S, Ebihara K, Sanaka T, Yamaguchi Y, Nakajima I, Kawai T, Yagisawa T, Honda H, Fuchinoue S, et al (1988). Effect of cyclosporine on proliferation of non-A, non-B hepatitis virus. Transplant Proc, 20(3 Suppl 3): 868–876

    PubMed  CAS  Google Scholar 

  • Tilton J C, Amrine-Madsen H, Miamidian J L, Kitrinos K M, Pfaff J, Demarest J F, Ray N, Jeffrey J L, Labranche C C, Doms RW (2010). HIV type 1 from a patient with baseline resistance to CCR5 antagonists uses drug-bound receptor for entry. AIDS Res Hum Retroviruses, 26(1): 13–24

    PubMed  CAS  Google Scholar 

  • Timpe J M, Stamataki Z, Jennings A, Hu K, Farquhar M J, Harris H J, Schwarz A, Desombere I, Roels G L, Balfe P, McKeating J A (2008). Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies. Hepatology, 47(1): 17–24

    PubMed  Google Scholar 

  • Trkola A, Kuhmann S E, Strizki J M, Maxwell E, Ketas T, Morgan T, Pugach P, Xu S, Wojcik L, Tagat J, Palani A, Shapiro S, Clader J W, McCombie S, Reyes G R, Baroudy B M, Moore J P (2002). HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. Proc Natl Acad Sci USA, 99(1): 395–400

    PubMed  CAS  Google Scholar 

  • Tu H, Gao L, Shi S T, Taylor D R, Yang T, Mircheff A K, Wen Y, Gorbalenya A E, Hwang S B, Lai M M (1999). Hepatitis C virus RNA polymerase and NS5A complex with a SNARE-like protein. Virology, 263(1): 30–41

    PubMed  CAS  Google Scholar 

  • Veazey R S, Ketas T J, Dufour J, Moroney-Rasmussen T, Green L C, Klasse P J, Moore J P (2010). Protection of rhesus macaques from vaginal infection by vaginally delivered maraviroc, an inhibitor of HIV-1 entry via the CCR5 co-receptor. J Infect Dis, 202(5): 739–744

    PubMed  CAS  Google Scholar 

  • Veedu R N, Wengel J (2010). Locked nucleic acids: promising nucleic acid analogs for therapeutic applications. Chem Biodivers, 7(3): 536–542

    PubMed  CAS  Google Scholar 

  • Vermeire K, Brouwers J, Van Herrewege Y, Le Grand R, Vanham G, Augustijns P, Bell T W, Schols D (2008). CADA, a potential anti-HIV microbicide that specifically targets the cellular CD4 receptor. Curr HIV Res, 6(3): 246–256

    PubMed  CAS  Google Scholar 

  • Vermeire K, Schols D (2005). Cyclotriazadisulfonamides: promising new CD4-targeted anti-HIV drugs. J Antimicrob Chemother, 56(2): 270–272

    PubMed  CAS  Google Scholar 

  • Vester B, Wengel J (2004). LNA (locked nucleic acid): high-affinity targeting of complementary RNA and DNA. Biochemistry, 43(42): 13233–13241

    PubMed  CAS  Google Scholar 

  • Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, Murthy K, Habermann A, Kräusslich H G, Mizokami M, Bartenschlager R, Liang T J (2005). Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med, 11(7): 791–796

    PubMed  CAS  Google Scholar 

  • Watashi K, Hijikata M, Hosaka M, Yamaji M, Shimotohno K (2003). Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. Hepatology, 38(5): 1282–1288

    PubMed  CAS  Google Scholar 

  • Watashi K, Ishii N, Hijikata M, Inoue D, Murata T, Miyanari Y, Shimotohno K (2005). Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. Mol Cell, 19(1): 111–122

    PubMed  CAS  Google Scholar 

  • Westby M, Lewis M, Whitcomb J, Youle M, Pozniak A L, James I T, Jenkins T M, Perros M, Van der Ryst E (2006). Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in a minority of HIV-1-infected patients following treatment with the CCR5 antagonist maraviroc is from a pretreatment CXCR4-using virus reservoir. J Virol, 80(10): 4909–4920

    PubMed  CAS  Google Scholar 

  • WHO/UNAIDS/UNICEF (2011). Progress Report 2011: Global HIV/AIDS Response. World Health Organization

  • Wilkin T J, Gulick R M (2012). CCR5 antagonism in HIV infection: current concepts and future opportunities. Annu Rev Med, 63(1): 81–93

    PubMed  CAS  Google Scholar 

  • Wilkin T J, Su Z, Kuritzkes D R, Hughes M, Flexner C, Gross R, Coakley E, Greaves W, Godfrey C, Skolnik P R, Timpone J, Rodriguez B, Gulick R M (2007). HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211. Clin Infect Dis, 44(4): 591–595

    PubMed  CAS  Google Scholar 

  • Yang F, Robotham J M, Nelson H B, Irsigler A, Kenworthy R, Tang H (2008). Cyclophilin A is an essential cofactor for hepatitis C virus infection and the principal mediator of cyclosporine resistance in vitro. J Virol, 82(11): 5269–5278

    PubMed  CAS  Google Scholar 

  • Zhang J, Randall G, Higginbottom A, Monk P, Rice C M, McKeating J A (2004). CD81 is required for hepatitis C virus glycoproteinmediated viral infection. J Virol, 78(3): 1448–1455

    PubMed  CAS  Google Scholar 

  • Zhao B, Mankowski M K, Snyder B A, Ptak R G, Liwang P J (2011). Highly potent chimeric inhibitors targeting two steps of HIV cell entry. J Biol Chem, 286(32): 28370–28381

    PubMed  CAS  Google Scholar 

  • Zhong J, Gastaminza P, Chung J, Stamataki Z, Isogawa M, Cheng G, McKeating J A, Chisari F V (2006). Persistent hepatitis C virus infection in vitro: coevolution of virus and host. J Virol, 80(22): 11082–11093

    PubMed  CAS  Google Scholar 

  • Zhou H, Xu M, Huang Q, Gates A T, Zhang X D, Castle J C, Stec E, Ferrer M, Strulovici B, Hazuda D J, Espeseth A S (2008). Genomescale RNAi screen for host factors required for HIV replication. Cell Host Microbe, 4(5): 495–504

    PubMed  CAS  Google Scholar 

  • Zhu H, Wong-Staal F, Lee H, Syder A, McKelvy J, Schooley R T, Wyles D L (2012). Evaluation of ITX 5061, a scavenger receptor B1 antagonist: resistance selection and activity in combination with other hepatitis C virus antivirals. J Infect Dis, 205(4): 656–662

    PubMed  CAS  Google Scholar 

  • Zou Y R, Kottmann A H, Kuroda M, Taniuchi I, Littman D R (1998). Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature, 393(6685): 595–599

    PubMed  CAS  Google Scholar 

  • Zydowsky L D, Etzkorn F A, Chang H Y, Ferguson S B, Stolz L A, Ho S I, Walsh C T (1992). Active site mutants of human cyclophilin A separate peptidyl-prolyl isomerase activity from cyclosporin A binding and calcineurin inhibition. Protein Sci, 1(9): 1092–1099

    PubMed  CAS  Google Scholar 

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Frausto, S., Lee, E. & Tang, H. Targeting host cofactors to inhibit viral infection. Front. Biol. 7, 445–458 (2012). https://doi.org/10.1007/s11515-012-1245-8

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Keywords

  • antiviral therapy
  • host-targeting
  • cofactors
  • drug resistance
  • HIV
  • HCV