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. 2009 Jan 6;126(9):341–348. [Article in Spanish] doi: 10.1157/13085735

Entrada del virus de la inmunodeficiencia humana en las células: mecanismos y posibilidades terapéuticas

HIV entry into the cells – mechanisms and therapeutic possibilities

Verónica Briz 1,⁎, Eva Poveda 1, Vicente Soriano 1
PMCID: PMC7131321  PMID: 16650368

Abstract

Human immunodeficiency virus (HIV) entry into cells is the first step in the viral replication cycle; which has been explored as a new therapeutic target; A better knowledge of the mechanisms involved in the entry process has led to the development of agents; which may inhibit each of the different steps of the viral entry process: attachment of the gp120 to the CD4 cell receptor; binding of the gp120 to CCR5 or CXCR4 coreceptors; and the fusion of viral and cell membranes; Entry inhibitors are the latest family of antiretroviral compounds; being enfuvirtide; a fusion inhibitor; the first approved; Several other entry inhibitors are currently in clinical development and hopefully soon will be part of the therapeutic armamentarium against HIV

Key words: HIV, Viral entry, Entry inhibitors, Enfuvirtide

Referencias bibliográficas

  • 1.Pallela F., Delaney K., Moorman A., Loveless M., Fuhrer J., Satten G. Declining morbidity and mortality among patients with advanced HIV infection. HIV outpatient study investigators. N Engl J Med. 1998;338:853–860. doi: 10.1056/NEJM199803263381301. [DOI] [PubMed] [Google Scholar]
  • 2.Shafer R., Winters M., Palmer S., Merigan T. Multiple concurrent reverse transcriptase and protease mutations and multidrug resistance of HIV-1 isolates from heavily treated patients. Ann Intern Med. 1998;128:906–911. doi: 10.7326/0003-4819-128-11-199806010-00008. [DOI] [PubMed] [Google Scholar]
  • 3.Little S., Holte S., Routy J., Daar E., Markowitz M., Collier A. Antiretroviral-drug resistance among patients recently infected with HIV. N Engl J Med. 2002;347:385–394. doi: 10.1056/NEJMoa013552. [DOI] [PubMed] [Google Scholar]
  • 4.Chan D., Kim P. HIV entry and its inhibition. Cell. 1998;93:681–684. doi: 10.1016/s0092-8674(00)81430-0. [DOI] [PubMed] [Google Scholar]
  • 5.Doms R. The plasma membrane as a combat zone in the HIV battlefield. Gen Dev. 2000;14:2677–2688. doi: 10.1101/gad.833300. [DOI] [PubMed] [Google Scholar]
  • 6.Fackler O., Peterlin B. Endocytic entry of HIV-1. Curr Biol. 2000;10:1005–1008. doi: 10.1016/s0960-9822(00)00654-0. [DOI] [PubMed] [Google Scholar]
  • 7.Granelli-Piperno A., Delgado E., Finkel V., Paxton W., Steinman R. Immature dendritic cells selectively replicate macrophagetropic (M-tropic) HIV type 1, while mature cells efficiently transmit both M- and T-tropic virus to T cells. J Virol. 1998;72:2733–2737. doi: 10.1128/jvi.72.4.2733-2737.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Lazzarin A., Clotet B., Cooper D., Reynes J., Arastéh K., Nelson M. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N Engl J Med. 2003;348:2186–2195. doi: 10.1056/NEJMoa035211. [DOI] [PubMed] [Google Scholar]
  • 9.Lalezari J., Henry M., O’Hearn M., Montaner J., Piliero P., Trottier B. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med. 2003;348:2175–2185. doi: 10.1056/NEJMoa035026. [DOI] [PubMed] [Google Scholar]
  • 10.Hallenberger S., Bosh V., Angliker H., Shaw W., Klenk H., Garten W. Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. Nature. 1992;360:358–361. doi: 10.1038/360358a0. [DOI] [PubMed] [Google Scholar]
  • 11.Dietrich U. HIV-1 Entry inhibitors. AIDS Rev. 2001;3:89–97. [Google Scholar]
  • 12.Weiss C. HIV-1 gp41: mediator of fusion and target for inhibition. AIDS Rev. 2003;5:214–221. [PubMed] [Google Scholar]
  • 13.Dalgleish A., Beverley P., Clapham P., Crawford D., Greaves M., Weiss R. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984;312:763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  • 14.Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984;312:767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  • 15.Sattentau Q., Weiss R. The CD4 antigen: physiological ligand and HIV receptor. Cell. 1988;52:631–633. doi: 10.1016/0092-8674(88)90397-2. [DOI] [PubMed] [Google Scholar]
  • 16.Hoxie J. Hypothetical assignment of intrachain disulfide bonds for HIV-2 and SIV envelope glycoproteins. AIDS Res Hum Retroviruses. 1991;7:495–499. doi: 10.1089/aid.1991.7.495. [DOI] [PubMed] [Google Scholar]
  • 17.Leonard C., Spellman M., Riddle L., Harris R., Thomas J., Gregory T. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant HIV envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem. 1990;265:10373–10382. [PubMed] [Google Scholar]
  • 18.Kowalski M., Potz J., Basiripour L., Dorfman T., Goh W., Terwilliger E. Functional regions of the envelope glycoprotein of HIV type 1. Science. 1987;237:1351–1355. doi: 10.1126/science.3629244. [DOI] [PubMed] [Google Scholar]
  • 19.Lasky L., Nakamura G., Smith D., Fennie C., Shimasaki C., Patzer E. Delineation of a region of the HIV type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell. 1987;50:975–985. doi: 10.1016/0092-8674(87)90524-1. [DOI] [PubMed] [Google Scholar]
  • 20.Madani N., Perdigoto A., Srinivasan K., Cox J., Chruma J., LaLone J. Localized changes in the gp120 envelope glycoprotein confer resistance to HIV entry inhibitors BMS-806 and #155. J Virol. 2004;78:3742–3752. doi: 10.1128/JVI.78.7.3742-3752.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Kwong P., Wyatt R., Robinson J., Sweet R., Sodroski J., Hendrickson W. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature. 1998;393:648–659. doi: 10.1038/31405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Myszka D., Sweet R., Hensley P., Brigham-Burke M., Kwong P., Hendrickson W. Energetics of the HIV gp120-CD4 binding reaction. Proc Natl Acad Sci USA. 2000;97:9026–9031. doi: 10.1073/pnas.97.16.9026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Allaway G., Davis-Bruno K., Beaudry G., García E., Wong E., Ryder A. Expression and characterization of CD4-IgG2, a novel heterotetramer that neutralizes primary HIV type 1 isolates. AIDS Res Hum Retroviruses. 1995;11:533–539. doi: 10.1089/aid.1995.11.533. [DOI] [PubMed] [Google Scholar]
  • 24.Jacobson J., Lowy I., Fletcher C., O’Neill T., Tran D., Ketas T. Singledose safety, pharmacology and antiviral activity of the HIV type 1 entry inhibitor PRO 542 in HIV-infected adults. J Infect Dis. 2000;182:326–329. doi: 10.1086/315698. [DOI] [PubMed] [Google Scholar]
  • 25.Castagna A., Biswas P., Beretta A., Lazzarin A. The appealing story of HIV entry inhibitors. From discovery of biological mechanisms to drug development. Drugs. 2005;65:879–904. doi: 10.2165/00003495-200565070-00001. [DOI] [PubMed] [Google Scholar]
  • 26.Nagashima K., Thompson D., Rosenfield S., Maddon P., Dragic T., Olson W. HIV type 1 entry inhibitors PRO 542 and T-20 are potently synergistic in blocking virus-cell and cell fusion. J Infect Dis. 2001;183:1121–1125. doi: 10.1086/319284. [DOI] [PubMed] [Google Scholar]
  • 27.Moore J., Sattentau Q., Klasse P., Burkly L. A monoclonal antibody to CD4 domain 2 blocks soluble CD4-induced conformational changes in the envelope glycoproteins of HIV-1 and HIV infection of CD4+ cells. J Virol. 1992;66:4784–4793. doi: 10.1128/jvi.66.8.4784-4793.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Vermeire K., Bell T., Chi H., Jin Q., Samala M., Sodoma A. The anti- HIV potency of cyclotriazadisulfonamide analogs is directly correlated with their ability to down-modulate the CD4 receptor. Mol Pharmacol. 2003;63:203–210. doi: 10.1124/mol.63.1.203. [DOI] [PubMed] [Google Scholar]
  • 29.Vermeire K., Zhang Y., Princen K., Hatse S., Samala M., Dey K. CADA inhibits HIV and human herpesvirus 7 replication by down-modulation of the cellular CD4 receptor. Virology. 2002;302:342–353. doi: 10.1006/viro.2002.1624. [DOI] [PubMed] [Google Scholar]
  • 30.Lin P., Robinson B., Gong Y., Ricarrdi Q., Guo C., Deminie C. Identification and characterization of a novel inhibitor of HIV-1 entry - I: virology and resistance [resumen 9]. Actas de 9th Conference on Retroviruses and Opportunistic Infections; febrero 24; Seattle; 2002. [Google Scholar]
  • 31.Lin P., Guo K., Fridell R., Ho H- T., Yamanaka G., Colonno R. Identification and characterization of a novel inhibitor of HIV-1 entry - II: mechanism of action [resumen 10]. Actas de 9th Conference on Retroviruses and Opportunistic Infections; febrero 24; Seattle; 2002. [Google Scholar]
  • 32.Feng Y., Broder C., Kennedy P., Berger E. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996;272:872–877. doi: 10.1126/science.272.5263.872. [DOI] [PubMed] [Google Scholar]
  • 33.Samson M., Labbe O., Mollereau C., Vassart G., Parmentier M. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry. 1996;35:3362–3367. doi: 10.1021/bi952950g. [DOI] [PubMed] [Google Scholar]
  • 34.Zhan Y., Lou B., Lal R., Gettie A., Marx P., Moore J. Use of inhibitors to evaluate coreceptor usage by simian and simian/human immunodeficiency viruses and HIV type 2 in primary cells. J Virol. 2000;74:6893–6910. doi: 10.1128/jvi.74.15.6893-6910.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Connor R., Sheridan K., Ceradini D., Choe S., Landau N. Change in coreceptor use coreceptor use correlates with disease progression in HIV-1- infected individuals. J Exp Med. 1997;185:621–628. doi: 10.1084/jem.185.4.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Comier E., Dragic T. The crown and stem of the V3 loop play distinct roles in HIV type 1 envelope glycoprotein interactions with the CCR5 coreceptor. J Virol. 2002;76:8953–8957. doi: 10.1128/JVI.76.17.8953-8957.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Sakaida H., Hori T., Yonezawa A., Sato A., Isaka Y., Yoshie O. T-tropic HIV-1-derived V3 loop peptides directly bind to CXCR4 and inhibit T-tropic HIV-1 infection. J Virol. 1998;72:9763–9770. doi: 10.1128/jvi.72.12.9763-9770.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Dragic T., Trkola A., Lin S., Nagashima F., Zhao L., Olson W. Aminoterminal substitutions in the CCR5 coreceptor impair gp120 binding and HIV type 1 entry. J Virol. 1998;72:279–285. doi: 10.1128/jvi.72.1.279-285.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Wu L., LaRosa G., Kassam N., Gordon C., Heath H., Ruffing N. Interaction of chemokine receptor CCR5 with its ligands: multiple domains for HIV-1 gp120 binding and a single domain for chemokine binding. J Exp Med. 1997;186:1373–1381. doi: 10.1084/jem.186.8.1373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Picard L., Wilkinson D., McKnight A., Gray P., Hoxie J., Clapham P. Role of the amino-terminal extracellular domain of CXCR4 in HIV type 1 entry. Virology. 1997;231:105–111. doi: 10.1006/viro.1997.8506. [DOI] [PubMed] [Google Scholar]
  • 41.Tsamis F., Gavrilov S., Kajumo F., Seibert C., Kuhmann S., Ketas T. Analysis of the mechanism by which the small-molecule CCR5 antagonists SCH-31125 and SCH-350581 inhibit HIV type 1 entry. J Virol. 2003;77:5201–5208. doi: 10.1128/JVI.77.9.5201-5208.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Watson C., Jenkinson S., Kazmierski W., Kenakin T. The CCR5 receptorbased mechanism of action of 873140, a potent allosteric noncompetitive HIV entry inhibitor. Mol Pharmacol. 2003;67:1268–1282. doi: 10.1124/mol.104.008565. [DOI] [PubMed] [Google Scholar]
  • 43.Murakami T., Nakajima T., Koyanagi Y., Tachibana K., Fujii N., Tamamura H. A small molecule CXCR4 inhibitor that blocks T cell line-tropic HIV-1 infection. J Exp Med. 1997;186:1389–1393. doi: 10.1084/jem.186.8.1389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Donzella G., Schols D., Lin S., Este J., Nagashima K., Maddon P. AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 coreceptor. Nature Med. 1998;4:72–77. doi: 10.1038/nm0198-072. [DOI] [PubMed] [Google Scholar]
  • 45.Labrosse B., Brelot N., Heveker N., Sol D., Schols E., De Clercq E. Determinants for sensitivity of HIV coreceptor CXCR4 to the bicyclam AMD3100. J Virol. 1998;72:6381–6388. doi: 10.1128/jvi.72.8.6381-6388.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Loetscher M., Geiser T., O’Reilly T., Zwahlen R., Baggiolini M., Moser B. Cloning of human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem. 1994;269:232–237. [PubMed] [Google Scholar]
  • 47.Brelot A., Heveker N., Pleskoff O., Sol N., Alizon M. Role of the first and third extracellular domains of CXCR4 in HIV coreceptor activity. J Virol. 1997;71:4744–4751. doi: 10.1128/jvi.71.6.4744-4751.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Baba M., Nishimura O., Kanzaki N., Okamoto M., Sawada H., Iizawa Y. A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc Natl Acad Sci USA. 1999;96:5698–5703. doi: 10.1073/pnas.96.10.5698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Dragic T., Trkola A., Thompson D., Comier E., Kajumo F., Maxwell E. A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proc Natl Acad Sci USA. 2000;97:5639–5644. doi: 10.1073/pnas.090576697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Lizawa Y., Kanzaki N., Takashima K., Miyake H., Tagawa Y., Sugihara Y. Anti-HIV-1 activity of TAK-220, a small molecule CCR5 antagonist [resumen 11]. Actas de 10th Conference on Retroviruses and Opportunistic Infections; febrero 10-14; Boston; 2003. [Google Scholar]
  • 51.Baba M., Kanzaki N., Miyake H., Wang X., Takashima K., Teshima K. RAK-652, a novel small molecule inhibitor of CCR5 antagonist with potent anti-HIV-1 activity [resumen 541]. Actas de 12th Conference on Retroviruses and Opportunistic Infections; febrero 10-14; Boston; 2003. [Google Scholar]
  • 52.Trkola A., Ketas T., Nagashima K., Zhao L., Cilliers T., Morris L. Potent, broad-spectrum inhibition of HIV type 1 by the CCR5 monoclonal antibody PRO 140. J Virol. 2001;75:579–588. doi: 10.1128/JVI.75.2.579-588.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Hitchcock C. The discovery and exploratory development of UK-427,857: a novel CCR5 antagonist for the treatment of HIV [resumen OP 4.5]. Actas de 13th International Symposium on HIV and Emerging Infectious Diseases; junio 3-5; Toulon; 2004. [Google Scholar]
  • 54.De Clercq E. New approaches toward anti-HIV chemotherapy. J Med Chem. 2005;10:241–274. doi: 10.1021/jm040158k. [DOI] [PubMed] [Google Scholar]
  • 55.Fätkenheuer G., Pozniak A., Johnson M., Plettenberg A., Staszewski S., Hoepelman I. Evaluation of dosing frequency and food effect on viral load reduction during short-term monotherapy with UK-427,857, a novel CCR5 antagonist [resumen B4489]. Actas de 15th International AIDS Conference; julio 11-16; Bangkok; 2004. [Google Scholar]
  • 56.Castonguay L., Weng Y., Adolfsen W., Di Salvo J., Kilburn R., Caldwell C. Binding of 2-aryl-4(piperidin-1yl)butanmines and 1, 3, 4-trisubstituted pyrrolidines to human CCR5: a molecular modeling-guide mutagenesis study of the binding pocket. Biochemistry. 2003;42:1544–1550. doi: 10.1021/bi026639s. [DOI] [PubMed] [Google Scholar]
  • 57.Maeda K., Nakata H., Miyakawa T., Gata H., Takaoka Y., Shibayama S. Spirodiketopiperazine-based CCR5 inhibitor, which preserves CC chemokine/ CCR5 interactions and exerts potent activity against R5 HIV type 1 in vitro. J Virol. 2004;78:8654–8662. doi: 10.1128/JVI.78.16.8654-8662.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Nakata H., Maeda K., Kawano Y., Miyakawa T., Shibayama S., Matsuo M. Potent in vivo anti-R5HIV effects of AK602, a novel spirodiketopiperazine (SPD)-containing HIV-specific CCR5 inhibitor, in hu-PBMCNOD- mice [resumen 564a]. Actas de 10th Conference on Retroviruses and Opportunistic Infections; febrero 10-14; Boston; 2003. [Google Scholar]
  • 59.Maeda K., Ogata H., Harada S., Miyakawa T., Nakata H., Koh Y. Determination of binding sites of a unique CCR5 inhibitor AK602 /ONO- 4128/ GW873140 on human CCR5 [resumen 540]. Actas de 11th Conference on Retroviruses and Opportunistic Infections; febrero 8-11; San Francisco; 2004. [Google Scholar]
  • 60.Schols D., Claes S., De Clercq E., Hendrix C., Bridger G., Calandra G. AMD-3100, a CXCR4 antagonist, reduced HIV viral load and X4 virus levels in humans [resumen 2]. Actas de 9th Conference on Retroviruses and Opportunistic Infections; febrero 24-28; Seattle; 2002. [Google Scholar]
  • 61.Schols D., Claes S., Hatse S., Princen K., Vermeire K., De Clercq E. Anti-HIV activity profile of AMD070, an orally bioavailable CXCR4 antagonist [resumen A39]. Actas de 16th International Conference on Antiviral Research; abril 27 a mayo 1; Savannah; 2003. [Google Scholar]
  • 62.Ichiyama K., Yokoyama-Kumakura S., Tanaka Y., Tanaka R., Hirose K., Bannai K. A diodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity. Proc Natl Acad Sci USA. 2003;100:4185–4190. doi: 10.1073/pnas.0630420100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Murakami E., Yoshida A., Kumakura S., Tanaka R., Mitsuhashi S., Hirose K. KRH-2731: an orally bioavailable CXCR4 antagonist in vivo [resumen LbA01]. Actas de 15th International AIDS Conference; Julio 11-16; Bangkok; 2004. [Google Scholar]
  • 64.Albert T. Structure of the leucine zipper. Curr Opin Gen Dev. 1992;2:205–210. doi: 10.1016/s0959-437x(05)80275-8. [DOI] [PubMed] [Google Scholar]
  • 65.Schulz T., Jameson B., Lopalco L., Siccarche A., Weiss R., Moore J. Conserved structural features in the interaction between retroviral surface and transmembrane glycoproteins. AIDS Res Hum Retroviruses. 1992;8:1571–1580. doi: 10.1089/aid.1992.8.1571. [DOI] [PubMed] [Google Scholar]
  • 66.Kilby J., Eron J. Novel therapies based on mechanisms of HIV-1 cell entry. N Engl J Med. 2003;348:2228–2238. doi: 10.1056/NEJMra022812. [DOI] [PubMed] [Google Scholar]
  • 67.Lu M., Blacklow S., Kim P. A trimeric structural domain of the HIV-1 transmembrane glycoprotein. Nature Struct Biol. 1995;2:1075–1082. doi: 10.1038/nsb1295-1075. [DOI] [PubMed] [Google Scholar]
  • 68.Cammack N. The potencial for HIV fusion inhibition. Curr Opin Infect Dis. 2001;14:13–16. doi: 10.1097/00001432-200102000-00003. [DOI] [PubMed] [Google Scholar]
  • 69.Mellikan G., Markosyan R., Hemmati H., Delmedico M., Lambert D., Cohen F. Evidence that the transition of HIV-1 gp41 into a six-helix bundle, not the bundle configuration, induces membrane fusion. J Cell Biol. 2000;151:413–423. doi: 10.1083/jcb.151.2.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Carr C., Kim P. A spring-loaded mechanism for the conformational change of influenza hemaglutinin. Cell. 1993;73:823–832. doi: 10.1016/0092-8674(93)90260-w. [DOI] [PubMed] [Google Scholar]
  • 71.Kliger Y., Levanon E. Cloaked similarity between HIV-1 and SARS-CoV suggest an anti-SARS strategy. BMC Microbiol. 2003;3:20. doi: 10.1186/1471-2180-3-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 72.Wild C., Oas T., McDanal D., Bolognesi D., Matthews T. A synthetic peptide inhibitor of HIV replication: correlation between solution structure and viral inhibition. Proc Natl Acad Sci USA. 1992;89:10537–10541. doi: 10.1073/pnas.89.21.10537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Wild C., Shugars D., Greenwell T., McDanal C., Matthews T. Peptides corresponding to a predictive alpha-helical domain of HIV type 1 are potent inhibitors of virus infection. Proc Natl Acad Sci USA. 1994;91:9770–9774. doi: 10.1073/pnas.91.21.9770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74.Jiang S., Li K., Strik N., Neurath A. HIV-1 inhibition by a peptide. Nature. 1993;365:113. doi: 10.1038/365113a0. [DOI] [PubMed] [Google Scholar]
  • 75.Wild C., Greenwell T., Matthews T. A synthetic peptide from HIV-1 gp41 is a potent inhibitor of virus mediated cell-cell fusion. AIDS Res Hum Retroviruses. 1993;9:1051–1053. doi: 10.1089/aid.1993.9.1051. [DOI] [PubMed] [Google Scholar]
  • 76.Poveda E., Rodés B., Toro C., Soriano V. Are fusion inhibitors active against all HIV variants? AIDS Res Hum Retroviruses. 2004;20:347–348. doi: 10.1089/088922204322996590. [DOI] [PubMed] [Google Scholar]
  • 77.Poveda E., Barreiro P., Rodés B., Soriano V. Enfuvirtide is active against HIV-1 type 1 group O. AIDS Res Hum Retroviruses. 2005;21:583–585. doi: 10.1089/aid.2005.21.583. [DOI] [PubMed] [Google Scholar]
  • 78.Witvrouw M., Pannecouque C., Switzer W., Folks T., De Clercq E., Heneine W. Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis. Antivir Ther. 2004;9:57–65. [PubMed] [Google Scholar]
  • 79.Wild C., Greenwell T., Shugars D., Rimsky-Clarke L., Matthews T. The inhibitory activity of an HIV type 1 peptide correlates with its ability to interact with a leucine zipper structure. AIDS Res Hum Retroviruses. 1995;11:323–325. doi: 10.1089/aid.1995.11.323. [DOI] [PubMed] [Google Scholar]
  • 80.Chen C., Matthews T., McDanal C., Bolognesi D., Greenberg M. A molecular clasp in the HIV type 1 TM protein determines the anti-HIV activity of gp41 derivates: implications for viral fusion. J Virol. 1995;69:3771–3777. doi: 10.1128/jvi.69.6.3771-3777.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81.Miralles G., Lalezari J., Bellos N., Richmond G., Zhang Y., Murchison H. T-1249 demonstrates potent antiviral activity over 10-day dosing in most patients who have failed a regimen containing enfuvirtide: planned interim analysis of T1249-102, a phase I/II stydy [resumen 14Ib]. Actas de 10th Conference on Retroviruses and Opportunistic Infections; febrero 10-14; Boston; 2003. [Google Scholar]
  • 82.Melby T., Zhang Y., Cammack N., Greenberg M., Miralles G. Genotypic and phenotypic evolution of virus envelope through 48 weeks of T-1249 treatment in the T1249-105 study [resumen 69]. Actas de XIV International HIV Drug Resistance Workshop; junio 7-11; Quebec; 2005. [Google Scholar]
  • 83.Clavel F., Hance A. HIV drug resistance. N Engl J Med. 2004;350:1023–1035. doi: 10.1056/NEJMra025195. [DOI] [PubMed] [Google Scholar]
  • 84.Wei X., Decker J., Liu H., Zhang Z., Arani R., Kilby J. Emergence of resistant HIV type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother. 2002;46:1896–1905. doi: 10.1128/AAC.46.6.1896-1905.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85.Greenberg M., Cammack N. Resistance to enfuvirtide, the first HIV fusion inhibitor. J Antimicrob Chemother. 2004;54:333–340. doi: 10.1093/jac/dkh330. [DOI] [PubMed] [Google Scholar]
  • 86.Poveda E., Rodés B., Labernardière J.L., Benito J.M., Toro C., González-Lahoz J. Evolution of genotypic and phenotypic resistance to enfuvirtide in HIV-infected patients experiencing prolonged virologic failure. J Med Virol. 2004;74:21–28. doi: 10.1002/jmv.20141. [DOI] [PubMed] [Google Scholar]
  • 87.Labrosse B., Labernardière J., Dam E., Trouplin V., Skrabal K., Clavel F. Baseline susceptibility of primary HIV-1 to entry inhibitors. J Virol. 2003;77:1610–1613. doi: 10.1128/JVI.77.2.1610-1613.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 88.Sista P., Melby T., Davison D., Jin L., Mosier S., Mink M. Characterization of determinants of genotypic and phenotypic resistance to enfuvirtide in baseline and on-treatment HIV-1 isolates. AIDS. 2004;18:1787–1794. doi: 10.1097/00002030-200409030-00007. [DOI] [PubMed] [Google Scholar]
  • 89.Stanfield-Oakley S., Jefrey J., McDanal C., Mosier S., Talton L., Jin L. Determinants of susceptibility to enfuvirtide map to gp41 in enfuvirtidenaive HIV-1. Antivir Ther. 2003;8:S22. [Google Scholar]
  • 90.Derdeyn C., Decker J., Sfakianos J., Zhang Z., O’Brian W., Ratner L. Sensitivity of HIV type 1 to fusion inhibitors targeted to the gp41 first heptad repeat involves distinct regions of gp41 and is consistently modulated by gp120 interactions with the coreceptor. J Virol. 2001;75:8605–8614. doi: 10.1128/JVI.75.18.8605-8614.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91.Reeves J., Gallo S., Ahmad N., Miamidian J., Harvey P., Sharron M. Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics. Proc Natl Acad Sci U S A. 2002;99:16249–16254. doi: 10.1073/pnas.252469399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 92.Whitcomb J., Huang W., Fransen S., Wrin T., Paxinos E., Toma J. Analysis of baseline enfuvirtide (T-20) susceptibility and co-receptor tropism in two phase III study populations [resumen 557]. Actas de 10th Conference on Retroviruses and Opportunistic Infections; febrero 10-14; Boston; 2003. [Google Scholar]
  • 93.Su C., Heilek-Snyder G., Fenger D., Ravindran P., Tsai K., Cammack N. The relationship between susceptibility to enfuvirtide of baseline viral recombinants and polymorphisms in the env region of R5-tropic HIV-1. Antivir Ther. 2003;8:S59. [Google Scholar]

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