The Lantibiotic Peptide Labyrinthopeptin A1 Demonstrates Broad Anti-HIV and Anti-HSV Activity with Potential for Microbicidal Applications

PLoS ONE

Volumn 8, Issue 5, 2013, Pages

  Férir, Geoffrey ^a   Petrova, Mariya I ^b,c   Andrei, Graciela ^a   Huskens, Dana ^a   Hoorelbeke, Bart ^a   Snoeck, Robert ^a   Vanderleyden, Jos ^b   Balzarini, Jan ^a   Bartoschek, Stefan ^d   Brönstrup, Mark ^d   Süssmuth, Roderich D ^e   Schols, Dominique ^a  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^b UNIVERSITY OF LEUVEN   (Belgium)

^c UNIVERSITY OF ANTWERP   (Belgium)

^d Sanofi R and D   (Germany)

^e TECHNISCHE UNIVERSITÄT BERLIN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CD69 ANTIGEN; GLYCOPROTEIN GP 120; INTERLEUKIN 2 RECEPTOR ALPHA; LABYRINTHOPEPTIN A1; LANTIBIOTIC; UNCLASSIFIED DRUG;

ANTIGEN EXPRESSION; ANTIVIRAL ACTIVITY; ARTICLE; BACTERIAL GROWTH; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG STRUCTURE; FEMALE; HERPES SIMPLEX VIRUS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; PROTEIN INTERACTION; UPREGULATION; VIRUS ATTACHMENT; VIRUS CELL INTERACTION; VIRUS REPLICATION; VIRUS TRANSMISSION;

ANTI-HIV AGENTS; ANTIGENS, CD4; BACTERIOCINS; CELL ADHESION MOLECULES; DRUG RESISTANCE, VIRAL; EPITHELIAL CELLS; FEMALE; GIANT CELLS; HIV ENVELOPE PROTEIN GP120; HIV INFECTIONS; HIV-1; HUMANS; KINETICS; LACTOBACILLUS; LECTINS, C-TYPE; LEUKOCYTES, MONONUCLEAR; NISIN; PROTEIN BINDING; RECEPTORS, CELL SURFACE; RECEPTORS, CXCR4; RECEPTORS, CXCR5; SIMPLEXVIRUS; VAGINA; VIRUS INTERNALIZATION; VIRUS REPLICATION;

HUMAN HERPESVIRUS 2; HUMAN IMMUNODEFICIENCY VIRUS 1; LACTOBACILLUS; SIMPLEXVIRUS;

EID: 84878408977     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0064010     Document Type: Article

References (57)

1. Available: http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/gr2012/20121120_UNAIDS_Global_Report_2012_en.pdf.Accessed 2012 Dec 14.
2. Shattock RJ, Rosenberg Z, (2012) Microbicides: topical prevention against HIV. Cold Spring Harb Perspect Med 4: a007385.
3. Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, et al. (2010) Effectiveness and safety of tenofovir gel, an antiretroviral microbicide for the prevention of HIV infection in women. Science 329: 1168-1174.
4. Celum CL, (2011) HIV preexposure prophylaxis: new data and potential use. Top Antivir Med 19: 181-185.
5. Nel AM, Coplan P, Smythe SC, McCord K, Mitchnick M, et al. (2010) Pharmacokinetic assessment of dapivirine vaginal microbicide gel in healthy, HIV-negative women. AIDS Res Hum Retroviruses 26: 1181-1190.
6. Romano J, Variano B, Coplan P, Van Roey J, Douville K, et al. (2010) Safety and availability of dapivirine (TMC120) delivered from an intravaginal ring. AIDS Res Hum Retroviruses 25: 483-488.
7. Shattock RJ, Moore JP, (2003) Inhibiting sexual transmission of HIV-1 infection. Nat Rev Microbiol 1: 25-34.
8. Ariën KK, Jespers V, Vanham G, (2011) HIV sexual transmission and microbicides. Rev Med Virol 21: 110-133.
9. Tilton JC, Doms RW, (2010) Entry inhibitors in the treatment of HIV-1 infection. Antiviral Res 85: 91-100.
10. Corey L, (2007) Synergistic copathogens - HIV-1 and HSV-2. N Engl J Med 356: 854-856.
11. Thurman AR, Doncel GF, (2012) Herpes simplex virus and HIV: genital infection synergy and novel approaches to dual prevention. Int J STD AIDS 23: 613-619.
12. Karasneh GA, Shukla D, (2011) Herpes simplex virus infects most cell types in vitro: clues to its success. Virol J 8: 841.
13. Connolly SA, Jackson JO, Jardetzky TS, Longnecker R, (2011) Fusing structure and function: a structural view of the herpesvirus entry machinery. Nat Rev Microbiol 9: 369-381.
14. Willey JM, van der Donk WA, (2007) Lantibiotics: peptides of diverse structure and function. Annu Rev Microbiol 61: 477-501.
15. Cotter PD, Hill C, Ross RP, (2005) Bacteriocins: developing innate immunity for food. Nat Rev Microbiol 3: 777-788.
16. Meindl K, Schmiederer T, Schneider K, Reicke A, Butz D, et al. (2010) Labyrinthopeptins: a new class of carbacyclic lantibiotics. Angew Chem Int Ed Engl 49: 1151-1154.
17. Seibert G, Vértesy L, Wink J, Winkler I, Süssmuth R, et al. (2008) WO2008/040469.
18. Wink J, Kroppenstedt RM, Seibert G, Stackebrandt E, (2003) Actinomadura namibiensis sp. nov. Int J Syst Evol Microbiol 53: 721-724.
19. Müller WM, Schmiederer T, Ensle P, Süssmuth RD, (2010) In vitro biosynthesis of the prepeptide of type-III lantibiotic labyrinthopeptin A2 including formation of a C-C bond as a post-translational modification. Angew Chem Int Ed Engl 49: 2436-2440.
20. Müller WM, Ensle P, Krawczyk B, Süssmuth RD, (2011) Leader peptide-directed processing of Labyrinthopeptin A2 precursor peptide by the modifying enzyme LabKC. Biochemistry 50: 8362-8373.
21. Krawczyk B, Ensle P, Müller W, Süssmuth RD, (2012) Deuterium labeled peptides give insights into the directionality of class III lantibiotic synthetase LabKC. JACS 134: 9922-9925.
22. Skinner MA, Ting R, Langlois AJ, Weinhold KJ, Lyerly HK, et al. (1988) Characteristics of a neutralizing monoclonal antibody to the HIV envelope glycoprotein. AIDS Res Hum Retroviruses 4: 187-197.
23. Schols D, Struyf S, Van Damme J, Esté JA, Henson G, et al. (1997) Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4. J Exp Med 186: 1383-1388.
24. Hoorelbeke B, Huskens D, Férir G, François KO, Takahashi A, et al. (2010) Actinohivin, a broadly neutralizing prokaryotic lectin, inhibits HIV-1 infection by specifically targeting high-mannose-type glycans on the gp120 envelope. Antimicrob Agents Chemother 54: 3287-3301.
25. Choi MH, Park YH, (2000) Selective control of lactobacilli in kimchi with nisin. Lett Appl Microbiol 30: 173-177.
26. Chun W, Hancock RE, (2000) Action of lysozyme and nisin mixtures against lactic acid bacteria. Int J Food Microbiol 60: 25-32.
27. Blower S, Ma L, (2004) Calculating the contribution of herpes simplex virus type 2 epidemics to increasing HIV incidence: treatment implications. Clin Infect Dis 39 (S5): S240-S247.
28. Abdool Karim SS, Richardson BA, Ramjee G, Hoffman IF, Chirenje ZM, et al. (2011) Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women. AIDS 25: 957-966.
29. Van Damme L, Ramjee G, Alary M, Vuylsteke B, Chandeying V, et al. (2002) Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial. Lancet 360: 971-977.
30. Balzarini J, Holý A, Jindrich J, Naesens L, Snoeck R, et al. (1993) Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine. Antimicrob Agents Chemother 37: 332-338.
31. Ying C, De Clercq E, Neyts J, (2000) Lamivudine, adefovir and tenofovir exhibit long-lasting anti-hepatitis B virus activity in cell culture. J Viral Hepat 7: 79-83.
32. Andrei G, Lisco A, Vanpouille C, Introini A, Balestra E, et al. (2011) Topical tenofovir, a microbicide effective against HIV, inhibits herpes simplex virus-2 replication. Cell Host Microbe 10: 379-389.
33. Geijtenbeek TB, Van Kooyk Y, (2003) DC-SIGN: a novel HIV receptor on DCs that mediates HIV-1 transmission. Curr Top Microbiol Immunol 276: 31-54.
34. Hladik F, McElrath MJ, (2008) Setting the stage: host invasion by HIV. Nat Rev Immunol 8: 447-457.
35. Princen K, Hatse S, Vermeire K, De Clercq E, Schols D, (2004) Evaluation of SDF-1/CXCR4-induced Ca2+ signaling by fluorometric imaging plate reader (FLIPR) and flow cytometry. Cytometry A 51: 35-45.
36. Centers for Disease Control and Prevention (CDC) (2012) Interim Guidance for Clinicians Considering the Use of Preexposure Prophylaxis for the Prevention of HIV Infection in Heterosexually Active Adults. MMWR Morb Mortal Wkly Rep 61: 586-589.
37. Chono K, Katsumata K, Suzuki H, Shiraki K, (2013) Synergistic activity of amenamevir (ASP2151) with nucleoside analogs against herpes simplex virus types 1 and 2 and varicella-zoster virus. Antiviral Res. 97: 154-160.
38. Mori T, O'keefe BR, Sowder RC 2nd, Bringans S, Gardella R, et al (2005) Isolation and characterization of griffithsin, a novel HIV-inactivating protein, from the red alga Griffithsia sp. J Biol Chem 280: 9345-9353.
39. Emau P, Tian B, O'keefe BR, Mori T, McMahon JB, et al. (2007) Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti-HIV microbicide. J Med Primatol 36: 244-253.
40. Huskens D, Vermeire K, Vandemeulebroucke E, Balzarini J, Schols D, (2008) Safety concerns for the potential use of cyanovirin-N as microbicidal anti-HIV agent. Int J Biochem Cell Biol 40: 2802-2814.
41. Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, et al. (2011) Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A 108Suppl 1: 4680-4687.
42. Ravel J, Gajer P, Li F, Mauck CK, Koenig SS, et al. (2012) Twice-daily application of HIV microbicides alter the vaginal microbiota. MBio 3: e00370-12.
43. Breukink E, De Kruijff B, (2006) Lipid II as target for antibiotics. Nat Rev Drug Discov 5: 321-332.
44. Aranha CC, Gupta SM, Reddy KV, (2008) Assessment of cervicovaginal cytokine levels following exposure to microbicide nisin gel in rabbits. Cytokine 43: 63-70.
45. Krawczyk JM, Völler GH, Krawczyk B, Kretz J, Brönstrup M, et al. (2013) Heterologous expression and engineering studies of labyrinthopeptins, new class III lantibiotics from Actinomadura namibiensis. Chem Biol. In press.
46. Lagenaur LA, Sanders-Beer BE, Brichacek B, Pal R, Liu X, et al. (2011) Prevention of vaginal SHIV transmission in macaques by a live recombinant Lactobacillus. Mucosal Immunol 4: 648-657.
47. Pauwels R, Andries K Desmyter J, Schols D, Kukla MJ, et al. (1990) Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives. Nature 343: 470-474.
48. Huskens D, Van Laethem K, Vermeire K, Balzarini J, Schols D, (2007) Resistance of HIV-1 to the broadly HIV-1-neutralizing, anti-carbohydrate antibody 2G12. Virology 360: 294-304.
49. De Vreese K, Kofler-Mongold V, Leutgeb C, Weber V, Vermeire K, et al. (1996) The molecular target of bicyclams, potent inhibitors of human immunodeficiency virus replication. J Virol 70: 689-696.
50. Goethals O, Vos A, Van Ginderen M, Geluykens P, Smits V, et al. (2010) Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles. Virology 402: 338-346.
51. Férir G, Hänchen A, François KO, Hoorelbeke B, Huskens D, et al. (2012) Feglymycin, a unique natural bacterial antibiotic peptide, inhibits HIV entry by targeting the viral envelope protein gp120. Virology 433: 308-319.
52. Vermeire K, Princen K, Hatse S, De Clercq E, Dey K, et al. (2004) CADA, a novel CD4-targeted HIV inhibitor, is synergistic with various anti-HIV drugs in vitro. AIDS 18: 2115-2125.
53. Férir G, Palmer KE, Schols D, (2012) Griffithsin, alone and combined with all classes of antiretroviral drugs, potently inhibits HIV cell-cell transmission and destruction of CD4+ T cells. J Antivir Antiretrovir. 4: 103-112.
54. Daelemans D, Pauwels R, De Clercq E, Pannecouque C, (2011) A time-of-drug addition approach to target identification of antiviral compounds. Nat Protoc 6: 925-933.
55. Férir G, Palmer KE, Schols D, (2011) Synergistic activity profile of griffithsin in combination with tenofovir, maraviroc and enfuvirtide against HIV-1 clade C. Virology. 417: 253-258.
56. Chou TC, Talalay P, (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drug or enzyme inhibitors. Adv Enzyme Regul 22: 27-55.
57. Chou TC, (2006) Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 58: 621-681.