Cationic host defence peptides: Potential as antiviral therapeutics

BioDrugs

Volumn 27, Issue 5, 2013, Pages 479-493

  Gwyer Findlay, Emily ^a   Currie, Silke M ^a   Davidson, Donald J ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA DEFENSIN; ANTIMICROBIAL CATIONIC PEPTIDE; ANTIVIRUS AGENT; BETA DEFENSIN; CATHELICIDIN; CATHELICIDIN ANTIMICROBIAL PEPTIDE LL 37; DEFENSIN; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 12P40; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; INTERLEUKIN 6; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; RANTES; THETA DEFENSIN; UNCLASSIFIED DRUG;

ANTIMICROBIAL ACTIVITY; ANTIVIRAL ACTIVITY; DRUG DESIGN; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; HERPES SIMPLEX VIRUS; HERPES SIMPLEX VIRUS 2; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOREGULATION; INFLUENZA VIRUS; INNATE IMMUNITY; NONHUMAN; PRIORITY JOURNAL; RESPIRATORY SYNCYTIAL PNEUMOVIRUS; REVIEW; VACCINIA VIRUS;

ANIMALS; ANTIVIRAL AGENTS; HUMANS; IMMUNITY, INNATE; PEPTIDES; VIRUS DISEASES;

EID: 84885142548     PISSN: 11738804     EISSN: 1179190X     Source Type: Journal    
DOI: 10.1007/s40259-013-0039-0     Document Type: Review

References (148)

1. Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, et al. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet. 2012;379(9832):2151-61.
2. De Clerq E. Antivirals: current state of the art. Future Virol. 2008;3(4):393-405.
3. Thakur N, Qureshi A, Kumar M. AVPpred: collection and prediction of highly effective antiviral peptides. Nucleic Acids Res. 2012;40(Web Server issue):W199-204.
4. Choi KY, Chow LN, Mookherjee N. Cationic host defence peptides: multifaceted role in immune modulation and inflammation. J Innate Immun. 2012;4(4):361-70.
5. Bowdish DM, Davidson DJ, Hancock RE. A re-evaluation of the role of host defence peptides in mammalian immunity. Curr Protein Pept Sci. 2005;6(1):35-51.
6. Beaumont PE, Li H, Davidson DJ. LL-37: an immunomodulatory antimicrobial host defence peptide. In: Zaat SAJ, Hiemstra PS, editors. Antimicrobial peptides and innate immunity. Progress in inflammation research. Basel: Springer; 2013. p. 97-122.
7. Zasloff M. Antimicrobial peptides of multicellular organisms. Nature. 2002;415(6870):389-95.
8. Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, et al. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985;76(4):1427-35.
9. Lehrer RI, Lu W. alpha-Defensins in human innate immunity. Immunol Rev. 2012;245(1):84-112.
10. Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol. 2003;3(9):710-20.
11. Lehrer RI, Cole AM, Selsted ME. theta-Defensins: cyclic peptides with endless potential. J Biol Chem. 2012;287(32):27014-9.
12. Ding J, Chou YY, Chang TL. Defensins in viral infections. J Innate Immun. 2009;1(5):413-20.
13. Rehaume LM, Hancock RE. Neutrophil-derived defensins as modulators of innate immune function. Crit Rev Immunol. 2008;28(3):185-200.
14. Tan BH, Meinken C, Bastian M, Bruns H, Legaspi A, Ochoa MT, et al. Macrophages acquire neutrophil granules for antimicrobial activity against intracellular pathogens. J Immunol. 2006;177(3):1864-71.
15. Jones DE, Bevins CL. Paneth cells of the human small intestine express an antimicrobial peptide gene. J Biol Chem. 1992;267(32):23216-25.
16. Mallow EB, Harris A, Salzman N, Russell JP, De Berardinis RJ, Ruchelli E, et al. Human enteric defensins. Gene structure and developmental expression. J Biol Chem. 1996;271(8):4038-45.
17. Quayle AJ, Porter EM, Nussbaum AA, Wang YM, Brabec C, Yip KP, et al. Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract. Am J Pathol. 1998;152(5):1247-58.
18. Klotman ME, Rapista A, Teleshova N, Micsenyi A, Jarvis GA, Lu W, et al. Neisseria gonorrhoeae-induced human defensins 5 and 6 increase HIV infectivity: role in enhanced transmission. J Immunol. 2008;180(9):6176-85.
19. Ouellette AJ, Selsted ME. Paneth cell defensins: endogenous peptide components of intestinal host defense. FASEB J. 1996;10(11):1280-9.
20. Eisenhauer PB, Lehrer RI. Mouse neutrophils lack defensins. Infect Immun. 1992;60(8):3446-7.
21. Shanahan MT, Tanabe H, Ouellette AJ. Strain-specific polymorphisms in Paneth cell alpha-defensins of C57BL/6 mice and evidence of vestigial myeloid alpha-defensin pseudogenes. Infect Immun. 2011;79(1):459-73.
22. Ericksen B, Wu Z, Lu W, Lehrer RI. Antibacterial activity and specificity of the six human {alpha}-defensins. Antimicrob Agents Chemother. 2005;49(1):269-75.
23. Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol. 2005;3(3):238-50.
24. Territo MC, Ganz T, Selsted ME, Lehrer R. Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest. 1989;84(6):2017-20.
25. Yang D, Chen Q, Chertov O, Oppenheim JJ. Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J Leukoc Biol. 2000;68(1):9-14.
26. Miles K, Clarke DJ, Lu W, Sibinska Z, Beaumont PE, Davidson DJ, et al. Dying and necrotic neutrophils are anti-inflammatory secondary to the release of alpha-defensins. J Immunol. 2009;183(3):2122-32.
27. Salzman NH, Hung K, Haribhai D, Chu H, Karlsson-Sjoberg J, Amir E, et al. Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol. 2010;11(1):76-83.
28. Chu H, Pazgier M, Jung G, Nuccio SP, Castillo PA, de Jong MF, et al. Human alpha-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets. Science. 2012;337(6093):477-81.
29. Semple CA, Gautier P, Taylor K, Dorin JR. The changing of the guard: molecular diversity and rapid evolution of beta-defensins. Mol Divers. 2006;10(4):575-84.
30. Zhao C, Wang I, Lehrer RI. Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett. 1996;396(2-3):319-22.
31. Duits LA, Ravensbergen B, Rademaker M, Hiemstra PS, Nibbering PH. Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells. Immunology. 2002;106(4):517-25.
32. Wehkamp J, Harder J, Wehkamp K, Wehkamp-von Meissner B, Schlee M, Enders C, et al. NF-kappaB- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium. Infect Immun. 2004;72(10):5750-8.
33. Voss E, Wehkamp J, Wehkamp K, Stange EF, Schroder JM, Harder J. NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2. J Biol Chem. 2006;281(4):2005-11.
34. Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ. Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol. 2004;22:181-215.
35. Schroeder BO, Wu Z, Nuding S, Groscurth S, Marcinowski M, Beisner J, et al. Reduction of disulphide bonds unmasks potent antimicrobial activity of human beta-defensin 1. Nature. 2011;469(7330):419-23.
36. Morrison G, Kilanowski F, Davidson D, Dorin J. Characterization of the mouse Beta defensin 1, defb1, mutant mouse model. Infect Immun. 2002;70(6):3053-60.
37. Moser C, Weiner DJ, Lysenko E, Bals R, Weiser JN, Wilson JM. beta-Defensin 1 contributes to pulmonary innate immunity in mice. Infect Immun. 2002;70(6):3068-72.
38. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, et al. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science. 1999;286(5439):525-8.
39. Hirsch T, Spielmann M, Zuhaili B, Fossum M, Metzig M, Koehler T, et al. Human beta-defensin-3 promotes wound healing in infected diabetic wounds. J Gene Med. 2009;11(3):220-8.
40. Semple F, Dorin JR. beta-Defensins: multifunctional modulators of infection, inflammation and more? J Innate Immun. 2012;4(4):337-48.
41. Selsted ME, Ouellette AJ. Mammalian defensins in the antimicrobial immune response. Nat Immunol. 2005;6(6):551-7.
42. Wang W, Owen SM, Rudolph DL, Cole AM, Hong T, Waring AJ, et al. Activity of alpha- and theta-defensins against primary isolates of HIV-1. J Immunol. 2004;173(1):515-20.
43. Nguyen TX, Cole AM, Lehrer RI. Evolution of primate theta-defensins: a serpentine path to a sweet tooth. Peptides. 2003;24(11):1647-54.
44. Tran D, Tran P, Roberts K, Osapay G, Schaal J, Ouellette A, et al. Microbicidal properties and cytocidal selectivity of rhesus macaque theta defensins. Antimicrob Agents Chemother. 2008;52(3):944-53.
45. Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol. 2004;75(1):39-48.
46. Sorensen O, Arnljots K, Cowland JB, Bainton DF, Borregaard N. The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils. Blood. 1997;90(7):2796-803.
47. Sorensen OE, Follin P, Johnsen AH, Calafat J, Tjabringa GS, Hiemstra PS, et al. Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood. 2001;97(12):3951-9.
48. Bowdish DM, Davidson DJ, Hancock RE. Immunomodulatory properties of defensins and cathelicidins. Curr Top Microbiol Immunol. 2006;306:27-66.
49. Frohm M, Agerberth B, Ahangari G, Stahle-Backdahl M, Liden S, Wigzell H, et al. The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. J Biol Chem. 1997;272(24):15258-63.
50. Dorschner RA, Pestonjamasp VK, Tamakuwala S, Ohtake T, Rudisill J, Nizet V, et al. Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus. J Invest Dermatol. 2001;117(1):91-7.
51. Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004;173(5):2909-12.
52. van der Does AM, Bergman P, Agerberth B, Lindbom L. Induction of the human cathelicidin LL-37 as a novel treatment against bacterial infections. J Leukoc Biol. 2012;92(4):735-42.
53. Nizet V, Ohtake T, Lauth X, Trowbridge J, Rudisill J, Dorschner RA, et al. Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature. 2001;414(6862):454-7.
54. Iimura M, Gallo RL, Hase K, Miyamoto Y, Eckmann L, Kagnoff MF. Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens. J Immunol. 2005;174(8):4901-7.
55. Kovach MA, Ballinger MN, Newstead MW, Zeng X, Bhan U, Yu FS, et al. Cathelicidin-related antimicrobial peptide is required for effective lung mucosal immunity in Gram-negative bacterial pneumonia. J Immunol. 2012;189(1):304-11.
56. De Y, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, et al. LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med. 2000;192(7):1069-74.
57. Scott MG, Davidson DJ, Gold MR, Bowdish D, Hancock RE. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol. 2002;169(7):3883-91.
58. Davidson DJ, Currie AJ, Reid GS, Bowdish DM, MacDonald KL, Ma RC, et al. The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J Immunol. 2004;172(2):1146-56.
59. Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007;449(7162):564-9.
60. Heilborn JD, Nilsson MF, Jimenez CI, Sandstedt B, Borregaard N, Tham E, et al. Antimicrobial protein hCAP18/LL-37 is highly expressed in breast cancer and is a putative growth factor for epithelial cells. Int J Cancer. 2005;114(5):713-9.
61. Koczulla R, Von Degenfeld G, Kupatt C, Krotz F, Zahler S, Gloe T, et al. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest. 2003;111(11):1665-72.
62. Li HN, Barlow PG, Bylund J, Mackellar A, Bjorstad A, Conlon J, et al. Secondary necrosis of apoptotic neutrophils induced by the human cathelicidin LL-37 is not proinflammatory to phagocytosing macrophages. J Leukoc Biol. 2009;86(4):891-902.
63. Barlow PG, Beaumont PE, Cosseau C, Mackellar A, Wilkinson TS, Hancock RE, et al. The human cathelicidin LL-37 preferentially promotes apoptosis of infected airway epithelium. Am J Respir Cell Mol Biol. 2010;43(6):692-702.
64. Daher KA, Selsted ME, Lehrer RI. Direct inactivation of viruses by human granulocyte defensins. J Virol. 1986;60(3):1068-74.
65. Hazrati E, Galen B, Lu W, Wang W, Ouyang Y, Keller MJ, et al. Human alpha- and beta-defensins block multiple steps in herpes simplex virus infection. J Immunol. 2006;177(12):8658-66.
66. Yasin B, Wang W, Pang M, Cheshenko N, Hong T, Waring AJ, et al. Theta defensins protect cells from infection by herpes simplex virus by inhibiting viral adhesion and entry. J Virol. 2004;78(10):5147-56.
67. Lehrer RI, Jung G, Ruchala P, Andre S, Gabius HJ, Lu W. Multivalent binding of carbohydrates by the human alpha-defensin, HD5. J Immunol. 2009;183(1):480-90.
68. Nakashima H, Yamamoto N, Masuda M, Fujii N. Defensins inhibit HIV replication in vitro. AIDS. 1993;7(8):1129.
69. Zhang L, Yu W, He T, Yu J, Caffrey RE, Dalmasso EA, et al. Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science. 2002;298(5595):995-1000.
70. Zhang L, Lopez P, He T, Yu W, Ho DD. Retraction of an interpretation. Science. 2004;303(5657):467.
71. Kuhn L, Trabattoni D, Kankasa C, Semrau K, Kasonde P, Lissoni F, et al. Alpha-defensins in the prevention of HIV transmission among breastfed infants. J Acquir Immune Defic Syndr. 2005;39(2):138-42.
72. Demirkhanyan LH, Marin M, Padilla-Parra S, Zhan C, Miyauchi K, Jean-Baptiste M, et al. Multifaceted mechanisms of HIV-1 entry inhibition by human alpha-defensin. J Biol Chem. 2012;287(34):28821-38.
73. Wu Z, Cocchi F, Gentles D, Ericksen B, Lubkowski J, Devico A, et al. Human neutrophil alpha-defensin 4 inhibits HIV-1 infection in vitro. FEBS Lett. 2005;579(1):162-6.
74. Chang TL, Vargas J Jr, DelPortillo A, Klotman ME. Dual role of alpha-defensin-1 in anti-HIV-1 innate immunity. J Clin Invest. 2005;115(3):765-73.
75. Furci L, Sironi F, Tolazzi M, Vassena L, Lusso P. Alpha-defensins block the early steps of HIV-1 infection: interference with the binding of gp120 to CD4. Blood. 2007;109(7):2928-35.
76. Guo CJ, Tan N, Song L, Douglas SD, Ho WZ. Alpha-defensins inhibit HIV infection of macrophages through upregulation of CC-chemokines. AIDS. 2004;18(8):1217-8.
77. Lawn SD, Butera ST, Folks TM. Contribution of immune activation to the pathogenesis and transmission of human immunodeficiency virus type 1 infection. Clin Microbiol Rev. 2001;14(4):753-77.
78. Hubert P, Herman L, Maillard C, Caberg JH, Nikkels A, Pierard G, et al. Defensins induce the recruitment of dendritic cells in cervical human papillomavirus-associated (pre)neoplastic lesions formed in vitro and transplanted in vivo. FASEB J. 2007;21(11):2765-75.
79. Rapista A, Ding J, Benito B, Lo YT, Neiditch MB, Lu W, et al. Human defensins 5 and 6 enhance HIV-1 infectivity through promoting HIV attachment. Retrovirology. 2011;8:45.
80. Schnapp D, Harris A. Antibacterial peptides in bronchoalveolar lavage fluid. Am J Respir Cell Mol Biol. 1998;19(3):352-6.
81. Ashitani J, Mukae H, Nakazato M, Ihi T, Mashimoto H, Kadota J, et al. Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse panbronchiolitis. Eur Respir J. 1998;11(1):104-11.
82. Singh PK, Jia HP, Wiles K, Hesselberth J, Liu L, Conway BA, et al. Production of beta-defensins by human airway epithelia. Proc Natl Acad Sci U S A. 1998;95(25):14961-6.
83. Hartshorn KL, White MR, Tecle T, Holmskov U, Crouch EC. Innate defense against influenza A virus: activity of human neutrophil defensins and interactions of defensins with surfactant protein D. J Immunol. 2006;176(11):6962-72.
84. Tecle T, White MR, Gantz D, Crouch EC, Hartshorn KL. Human neutrophil defensins increase neutrophil uptake of influenza A virus and bacteria and modify virus-induced respiratory burst responses. J Immunol. 2007;178(12):8046-52.
85. Leikina E, Delanoe-Ayari H, Melikov K, Cho MS, Chen A, Waring AJ, et al. Carbohydrate-binding molecules inhibit viral fusion and entry by crosslinking membrane glycoproteins. Nat Immunol. 2005;6(10):995-1001.
86. Caton AJ, Brownlee GG, Yewdell JW, Gerhard W. The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell. 1982;31(2 Pt 1):417-27.
87. Salvatore M, Garcia-Sastre A, Ruchala P, Lehrer RI, Chang T, Klotman ME. alpha-Defensin inhibits influenza virus replication by cell-mediated mechanism(s). J Infect Dis. 2007;196(6):835-43.
88. Sieczkarski SB, Brown HA, Whittaker GR. Role of protein kinase C betaII in influenza virus entry via late endosomes. J Virol. 2003;77(1):460-9.
89. Doss M, White MR, Tecle T, Gantz D, Crouch EC, Jung G, et al. Interactions of alpha-, beta-, and theta-defensins with influenza A virus and surfactant protein D. J Immunol. 2009;182(12):7878-87.
90. Smith JG, Nemerow GR. Mechanism of adenovirus neutralization by human alpha-defensins. Cell Host Microbe. 2008;3(1):11-9.
91. Gropp R, Frye M, Wagner TO, Bargon J. Epithelial defensins impair adenoviral infection: implication for adenovirus-mediated gene therapy. Hum Gene Ther. 1999;10(6):957-64.
92. Buck CB, Day PM, Thompson CD, Lubkowski J, Lu W, Lowy DR, et al. Human alpha-defensins block papillomavirus infection. Proc Natl Acad Sci U S A. 2006;103(5):1516-21.
93. Dugan AS, Maginnis MS, Jordan JA, Gasparovic ML, Manley K, Page R, et al. Human alpha-defensins inhibit BK virus infection by aggregating virions and blocking binding to host cells. J Biol Chem. 2008;283(45):31125-32.
94. Smith JG, Silvestry M, Lindert S, Lu W, Nemerow GR, Stewart PL. Insight into the mechanisms of adenovirus capsid disassembly from studies of defensin neutralization. PLoS Pathog. 2010;6(6):e1000959.
95. Bastian A, Schafer H. Human alpha-defensin 1 (HNP-1) inhibits adenoviral infection in vitro. Regul Pept. 2001;101(1-3):157-61.
96. Harvey SA, Romanowski EG, Yates KA, Gordon YJ. Adenovirus-directed ocular innate immunity: the role of conjunctival defensin-like chemokines (IP-10, I-TAC) and phagocytic human defensin-alpha. Invest Ophthalmol Vis Sci. 2005;46(10):3657-65.
97. Gounder AP, Wiens ME, Wilson SS, Lu W, Smith JG. Critical determinants of human alpha-defensin 5 activity against non-enveloped viruses. J Biol Chem. 2012;287(29):24554-62.
98. Nguyen EK, Nemerow GR, Smith JG. Direct evidence from single-cell analysis that human {alpha}-defensins block adenovirus uncoating to neutralize infection. J Virol. 2010;84(8):4041-9.
99. Chong KT, Thangavel RR, Tang X. Enhanced expression of murine beta-defensins (MBD-1, -2,- 3, and -4) in upper and lower airway mucosa of influenza virus infected mice. Virology. 2008;380(1):136-43.
100. Quinones-Mateu ME, Lederman MM, Feng Z, Chakraborty B, Weber J, Rangel HR, et al. Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication. AIDS. 2003;17(16):F39-48.
101. Duits LA, Nibbering PH, van Strijen E, Vos JB, Mannesse-Lazeroms SP, van Sterkenburg MA, et al. Rhinovirus increases human beta-defensin-2 and -3 mRNA expression in cultured bronchial epithelial cells. FEMS Immunol Med Microbiol. 2003;38(1):59-64.
102. Proud D, Sanders SP, Wiehler S. Human rhinovirus infection induces airway epithelial cell production of human beta-defensin 2 both in vitro and in vivo. J Immunol. 2004;172(7):4637-45.
103. Kota S, Sabbah A, Chang TH, Harnack R, Xiang Y, Meng X, et al. Role of human beta-defensin-2 during tumor necrosis factor-alpha/NF-kappaB-mediated innate antiviral response against human respiratory syncytial virus. J Biol Chem. 2008;283(33):22417-29.
104. Nittayananta W, Kemapunmanus M, Amornthatree K, Talungchit S, Sriplung H. Oral human beta-defensin 2 in HIV-infected subjects with long-term use of antiretroviral therapy. J Oral Pathol Med. 2013;42(1):53-60.
105. Sun L, Finnegan CM, Kish-Catalone T, Blumenthal R, Garzino-Demo P, La Terra Maggiore GM, et al. Human beta-defensins suppress human immunodeficiency virus infection: potential role in mucosal protection. J Virol. 2005;79(22):14318-29.
106. Feng Z, Dubyak GR, Lederman MM, Weinberg A. Cutting edge: human beta defensin 3 - a novel antagonist of the HIV-1 coreceptor CXCR4. J Immunol. 2006;177(2):782-6.
107. Hardwick RJ, Amogne W, Mugusi S, Yimer G, Ngaimisi E, Habtewold A, et al. beta-Defensin genomic copy number is associated with HIV load and immune reconstitution in sub-saharan Africans. J Infect Dis. 2012;206(7):1012-9.
108. Zapata W, Rodriguez B, Weber J, Estrada H, Quinones-Mateu ME, Zimermman PA, et al. Increased levels of human beta-defensins mRNA in sexually HIV-1 exposed but uninfected individuals. Curr HIV Res. 2008;6(6):531-8.
109. Ryan LK, Dai J, Yin Z, Megjugorac N, Uhlhorn V, Yim S, et al. Modulation of human beta-defensin-1 (hBD-1) in plasmacytoid dendritic cells (PDC), monocytes, and epithelial cells by influenza virus, Herpes simplex virus, and Sendai virus and its possible role in innate immunity. J Leukoc Biol. 2011;90(2):343-56.
110. Gong T, Jiang Y, Wang Y, Yang D, Li W, Zhang Q, et al. Recombinant mouse beta-defensin 2 inhibits infection by influenza A virus by blocking its entry. Arch Virol. 2010;155(4):491-8.
111. Jiang Y, Yang D, Li W, Wang B, Jiang Z, Li M. Antiviral activity of recombinant mouse beta-defensin 3 against influenza A virus in vitro and in vivo. Antivir Chem Chemother. 2012;22(6):255-62.
112. Becker S, Quay J, Soukup J. Cytokine (tumor necrosis factor, IL-6, and IL-8) production by respiratory syncytial virus-infected human alveolar macrophages. J Immunol. 1991;147(12):4307-12.
113. Howell MD, Streib JE, Leung DY. Antiviral activity of human beta-defensin 3 against vaccinia virus. J Allergy Clin Immunol. 2007;119(4):1022-5.
114. Howell MD, Jones JF, Kisich KO, Streib JE, Gallo RL, Leung DY. Selective killing of vaccinia virus by LL-37: implications for eczema vaccinatum. J Immunol. 2004;172(3):1763-7.
115. Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 2003;171(6):3262-9.
116. Tang YQ, Yuan J, Osapay G, Osapay K, Tran D, Miller CJ, et al. A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins. Science. 1999;286(5439):498-502.
117. Cole AM, Hong T, Boo LM, Nguyen T, Zhao C, Bristol G, et al. Retrocyclin: a primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1. Proc Natl Acad Sci USA. 2002;99(4):1813-8.
118. Brandt CR, Akkarawongsa R, Altmann S, Jose G, Kolb AW, Waring AJ, et al. Evaluation of a theta-defensin in a murine model of herpes simplex virus type 1 keratitis. Invest Ophthalmol Vis Sci. 2007;48(11):5118-24.
119. Munk C, Wei G, Yang OO, Waring AJ, Wang W, Hong T, et al. The theta-defensin, retrocyclin, inhibits HIV-1 entry. AIDS Res Hum Retroviruses. 2003;19(10):875-81.
120. Gallo SA, Wang W, Rawat SS, Jung G, Waring AJ, Cole AM, et al. Theta-defensins prevent HIV-1 Env-mediated fusion by binding gp41 and blocking 6-helix bundle formation. J Biol Chem. 2006;281(27):18787-92.
121. Owen SM, Rudolph DL, Wang W, Cole AM, Waring AJ, Lal RB, et al. RC-101, a retrocyclin-1 analogue with enhanced activity against primary HIV type 1 isolates. AIDS Res Hum Retroviruses. 2004;20(11):1157-65.
122. Cole AL, Yang OO, Warren AD, Waring AJ, Lehrer RI, Cole AM. HIV-1 adapts to a retrocyclin with cationic amino acid substitutions that reduce fusion efficiency of gp41. J Immunol. 2006;176(11):6900-5.
123. Gupta P, Ratner D, Ding M, Patterson B, Rohan LC, Reinhart TA, et al. Retrocyclin RC-101 blocks HIV-1 transmission across cervical mucosa in an organ culture. J Acquir Immune Defic Syndr. 2012;60(5):455-61.
124. Cole AM, Patton DL, Rohan LC, Cole AL, Cosgrove-Sweeney Y, Rogers NA, et al. The formulated microbicide RC-101 was safe and antivirally active following intravaginal application in pigtailed macaques. PLoS One. 2010;5(11):e15111.
125. Liang QL, Zhou K, He HX. Retrocyclin 2: a new therapy against avian influenza H5N1 virus in vivo and vitro. Biotechnol Lett. 2010;32(3):387-92.
126. Doss M, Ruchala P, Tecle T, Gantz D, Verma A, Hartshorn A, et al. Hapivirins and diprovirins: novel theta-defensin analogs with potent activity against influenza A virus. J Immunol. 2012;188(6):2759-68.
127. Miura TA, Holmes KV. Host-pathogen interactions during coronavirus infection of primary alveolar epithelial cells. J Leukoc Biol. 2009;86(5):1145-51.
128. Wohlford-Lenane CL, Meyerholz DK, Perlman S, Zhou H, Tran D, Selsted ME, et al. Rhesus theta-defensin prevents death in a mouse model of severe acute respiratory syndrome coronavirus pulmonary disease. J Virol. 2009;83(21):11385-90.
129. Malm J, Sorensen O, Persson T, Frohm-Nilsson M, Johansson B, Bjartell A, et al. The human cationic antimicrobial protein (hCAP-18) is expressed in the epithelium of human epididymis, is present in seminal plasma at high concentrations, and is attached to spermatozoa. Infect Immun. 2000;68(7):4297-302.
130. Levinson P, Kaul R, Kimani J, Ngugi E, Moses S, MacDonald KS, et al. Levels of innate immune factors in genital fluids: association of alpha defensins and LL-37 with genital infections and increased HIV acquisition. AIDS. 2009;23(3):309-17.
131. Levinson P, Choi RY, Cole AL, Hirbod T, Rhedin S, Payne B, et al. HIV-neutralizing activity of cationic polypeptides in cervicovaginal secretions of women in HIV-serodiscordant relationships. PLoS One. 2012;7(2):e31996.
132. Bergman P, Walter-Jallow L, Broliden K, Agerberth B, Soderlund J. The antimicrobial peptide LL-37 inhibits HIV-1 replication. Curr HIV Res. 2007;5(4):410-5.
133. Wong JH, Legowska A, Rolka K, Ng TB, Hui M, Cho CH, et al. Effects of cathelicidin and its fragments on three key enzymes of HIV-1. Peptides. 2011;32(6):1117-22.
134. Barlow PG, Svoboda P, Mackellar A, Nash AA, York IA, Pohl J, et al. Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37. PLoS One. 2011;6(10):e25333.
135. Tripathi S, Tecle T, Verma A, Crouch E, White M, Hartshorn KL. The human cathelicidin LL-37 inhibits influenza A viruses through a mechanism distinct from that of surfactant protein D or defensins. J Gen Virol. 2013;94(Pt 1):40-9.
136. Mookherjee N, Brown KL, Bowdish DM, Doria S, Falsafi R, Hokamp K, et al. Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. J Immunol. 2006;176(4):2455-64.
137. Xagorari A, Chlichlia K. Toll-like receptors and viruses: induction of innate antiviral immune responses. Open Microbiol J. 2008;2:49-59.
138. Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, Facchinetti V, et al. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med. 2009;206(9):1983-94.
139. Lai Y, Adhikarakunnathu S, Bhardwaj K, Ranjith-Kumar CT, Wen Y, Jordan JL, et al. LL37 and cationic peptides enhance TLR3 signaling by viral double-stranded RNAs. PLoS One. 2011;6(10):e26632.
140. Filewod NC, Pistolic J, Hancock RE. Low concentrations of LL-37 alter IL-8 production by keratinocytes and bronchial epithelial cells in response to proinflammatory stimuli. FEMS Immunol Med Microbiol. 2009;56(3):233-40.
141. Hasan M, Ruksznis C, Wang Y, Leifer CA. Antimicrobial peptides inhibit polyinosinic-polycytidylic acid-induced immune responses. J Immunol. 2011;187(11):5653-9.
142. Hansdottir S, Monick MM, Hinde SL, Lovan N, Look DC, Hunninghake GW. Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol. 2008;181(10):7090-9.
143. Mansbach JM, Piedra PA, Borregaard N, Martineau AR, Neuman MI, Espinola JA, et al. Serum cathelicidin level is associated with viral etiology and severity of bronchiolitis. J Allergy Clin Immunol. 2012;130(4):1007 e1-1008 e1.
144. Currie SM, Gwyer Findlay E, McHugh B, Mackellar A, Tian M, Wang H, et al. The human cathelicidin LL-37 has antiviral properties against respiratory syncytial virus. Manuscript under revisions. 2013.
145. Schauber J, Gallo RL. Antimicrobial peptides and the skin immune defense system. J Allergy Clin Immunol. 2008;122(2):261-6.
146. Howell MD, Gallo RL, Boguniewicz M, Jones JF, Wong C, Streib JE, et al. Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity. 2006;24(3):341-8.
147. Dean RE, O'Brien LM, Thwaite JE, Fox MA, Atkins H, Ulaeto DO. A carpet-based mechanism for direct antimicrobial peptide activity against vaccinia virus membranes. Peptides. 2010;31(11):1966-72.
148. Varkey J, Nagaraj R. Antibacterial activity of human neutrophil defensin HNP-1 analogs without cysteines. Antimicrob Agents Chemother. 2005;49(11):4561-6.