期刊论文详细信息
Virology Journal
Structural characteristics and antiviral activity of multiple peptides derived from MDV glycoproteins B and H
Ming Wang1  Xiaojing Chi1  Xiaojia Wang1 
[1] Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, No. 2, Yuan Ming Yuan West Road, Haidian District, Beijing 100193, PR China
关键词: viral entry mechanism;    antiviral inhibitor;    structural characteristics;    chorioallantoic membrane;    plaque formation;    glycoprotein;    Marek's disease virus;   
Others  :  1156783
DOI  :  10.1186/1743-422X-8-190
 received in 2011-01-14, accepted in 2011-04-25,  发布年份 2011
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【 摘 要 】

Background

Marek's disease virus (MDV), which is widely considered to be a natural model of virus-induced lymphoma, has the potential to cause tremendous losses in the poultry industry. To investigate the structural basis of MDV membrane fusion and to identify new viral targets for inhibition, we examined the domains of the MDV glycoproteins gH and gB.

Results

Four peptides derived from the MDV glycoprotein gH (gHH1, gHH2, gHH3, and gHH5) and one peptide derived from gB (gBH1) could efficiently inhibit plaque formation in primary chicken embryo fibroblast cells (CEFs) with 50% inhibitory concentrations (IC50) of below 12 μM. These peptides were also significantly able to reduce lesion formation on chorioallantoic membranes (CAMs) of infected chicken embryos at a concentration of 0.5 mM in 60 μl of solution. The HR2 peptide from Newcastle disease virus (NDVHR2) exerted effects on MDV specifically at the stage of virus entry (i.e., in a cell pre-treatment assay and an embryo co-treatment assay), suggesting cross-inhibitory effects of NDV HR2 on MDV infection. None of the peptides exhibited cytotoxic effects at the concentrations tested. Structural characteristics of the five peptides were examined further.

Conclusions

The five MDV-derived peptides demonstrated potent antiviral activity, not only in plaque formation assays in vitro, but also in lesion formation assays in vivo. The present study examining the antiviral activity of these MDV peptides, which are useful as small-molecule antiviral inhibitors, provides information about the MDV entry mechanism.

【 授权许可】

   
2011 Wang et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Eckert DM, Kim PS: Mechanisms of viral membrane fusion and its inhibition. Ann Rev Biochem 2001, 70:777-810.
  • [2]Heldwein EE, Krummenacher C: Entry of herpesviruses into mammalian cells. Cell Mol Life Sci 2008, 65:1653-68.
  • [3]Backovic M, Jardetzky TS: Class III viral membrane fusion proteins. Curr Opin Struct Biol 2009, 19:189-96.
  • [4]Heldwein EE, Lou H, Bender FC, Cohen GH, Eisenberg RJ, Harrison SC: Crystal structure of glycoprotein B from herpes simplex virus 1. Science 2006, 313:217-20.
  • [5]Chowdary TK, Cairns TM, Atanasiu D, Cohen GH, Eisenberg RJ, Heldwein EE: Crystal structure of the conserved herpesvirus fusion regulator complex gH-gL. Nat Struct Mol Biol 2010, 17:882-8.
  • [6]Campadelli-Fiume G, Amasio M, Avitabile E, Cerretani A, Forghieri C, Gianni T, Menotti L: The multipartite system that mediates entry of herpes simplex virus into the cell. Rev Med Virol 2007, 17:313-26.
  • [7]Gianni T, Forghieri C, Campadelli-Fiume G: The herpesvirus glycoproteins B and H.L are sequentially recruited to the receptor-bound gD to effect membrane fusion at virus entry. Proc Natl Acad Sci USA 2007, 104:3668-73.
  • [8]Kirschner AN, Omerovic J, Popov B, Longnecker RL, Jadetzky TS: Soluble Epstein-Barr virus glycoproteins gH, gL, and gp42 form a 1:1:1 stable complex that acts like soluble gp42 in B-cell fusion but not in epithelial cell fusion. J Virol 2006, 80:9444-9454.
  • [9]Ryckman BJ, Rainish BL, Chase MC: Characterization of the human cytomegalovirus gH/gL/UL128-31 complex that mediates entry into epithelial and endothelial cells. J Virol 2008, 82:60-70.
  • [10]Galdiero S, Falanga A, Vitiello M, Browne H, Pedone C, Galdiero M: Fusogenic domains in herpes simplex virus type 1 glycoptein H. J Boil Chem 2005, 280:28632-43.
  • [11]Galdiero S, Vitiello M, D'Isanto M, Falanga A, CollinS C, Raieta K, Pedone C, Browne H, Galdiero M: Analysis of synthetic peptides from heptad-repeat domains of herpes simplex virus type 1 glycoproteins H and B. J Gen Virol 2006, 87:1085-97.
  • [12]Lopper M, Compton T: Coiled-coil domains in glycoproteins B and H are involved in human cytomegalovirus membrane fusion. J Virol 2004, 78:8333-41.
  • [13]Akkarawongsa R, Pocaro NE, Case G, Kolb AW, Brandt CR: Multiple peptides homologous to herpes simplex virus type 1 glycoprotein B inhibit viral infection. Antimicrob Agents Chemother 2009, 53:987-996.
  • [14]Backovic M, Jardetzky TS, Longnecker R: Hydrophobic residues that form putative fusion loops of Epstein-Barr virus glycoprotein B are critical for fusion activity. J Virol 2007, 81:9596-9600.
  • [15]Galdiero S, Vitiello M, D'Isanto M, Falanga A, Cantisan M, Browne H, Pedone C, Galdiero M: The identification and characterization of fusogenic domains in herpes virus glycoprotein B molecules. Chembiochem 2008, 9:758-67.
  • [16]Gianni T, Martelli PL, Casadio R, Campadelli-Fiume G: The ectodomain of herpes simplex virus glycoprotein H contains a membrane α-helix with attributes of an internal fusion peptide, positionally conserved in the Herpesviridae family. J Virol 2005, 79:2931-2940.
  • [17]Osterrieder N, Kamil JP, Schumacher D, Tischer BK, Trapp S: Marek's disease virus: from miasma to model. Nat Rev Microbiol 2006, 4:283-294.
  • [18]Jarosinski KW, Tischer BK, Trapp S, Osterrieder N: Marek's disease virus: lytic replication, oncogenesis and control. Expert Rev Vaccines 2006, 5:761-72.
  • [19]Calnek BW, Witter RL: Neoplasic disease/Marek disease, in disease of poultry. IA: Iowa State University Press, Ames; 1991:342-385.
  • [20]Wu P, Reed WM, Lee LF: Glycoproteins H and L of Marek's disease virus form a hetero-oligomer essential for translocation and cell surface expression. Arch Virol 2001, 146:983-92.
  • [21]Yoshida S, Lee LF, Yanagida N, Nazerian K: Mutational analysis of the proteolytic cleavage site of glycoprotein B (gB) of Marek's disease virus. Gene 1994, 150:303-6.
  • [22]Ding J, Cui Z, Jiang S, Li Y: Study on the structure of heteropolymer pp38/pp24 and its enhancement on the bi-directional promoter upstream of pp38 gene in Marek's disease virus. Sci China C Life Sci 2008, 51:821-6.
  • [23]Galdiero S, Falanga A, Vitiello M, D'Isanto M, Cantisani M, Kampanaraki A, Benedetti E, Browne H, Galdiero M: Peptides containing membrane-interacting motifs inhibit herpes simplex virus type 1 infectivity. Peptides 2008, 29:1461-71.
  • [24]Lee S, Ohashi K, Sugimoto C, Onuma M: Heparin inhibits plaque formation by cell-free Marek's disease viruses in vitro. J Vet Med Sci 2001, 63:427-32.
  • [25]Woodruff AM, Goodpasture EW: The susceptibility of the chorio-allantoic membrane of chick embryos to infection with the fowl-pox virus. Am J Pathol 1931, 7:209-222.
  • [26]Scher C, Haudenschild C, Klagsbrun M: The chick chorioallantoic membrane as a model system for the study of tissue invasion by viral transformed cells. Cell 1976, 8:373-82.
  • [27]Siegel BV, Batts AA: Patterns of avian viral multiplication and associated membrane histopathology in the chorioallantois of developing chick embryo. Arch Gesamte Virusforsch 1957, 7:498-505.
  • [28]Sharma JM, Coulson BD, Young E: Effect of in vitro adaptation of Marek's disease virus on pock induction on the chorioallantoic membrane of embryonated chicken eggs. Infect Immun 1976, 13:292-295.
  • [29]Longenecker BM, Pazderka F, Stone HS, Gavora JS, Ruth RF: In ovo assay for Marek's disease virus and turkey herpesvirus. Infect Immun 1975, 11:922-31.
  • [30]Buranathai C, Rodriguez J, Grose C: Transformation of primary chick embryo fibroblasts by Marek's disease virus. Virology 1997, 239:20-35.
  • [31]Yakovleva LS, Mazurenko NP, Gunenkova NK, Vinogradov VN, Pavlovskaya AI, Chernyakhovskaya IY: Marek's disease virus (Kekava strain) replication in chickens, chick embryos and cell cultures. Acta Virol 1975, 19:293-8.
  • [32]Wang XJ, Bai YD, Zhang GZ, Wang M, Gao GF: Structure and function study of paramyxovirus fusion protein heptad repeat peptides. Arch Biochem Biophys 2005, 436:316-322.
  • [33]Okazaki K, Kida H: A synthetic peptide from a heptad repeat region of herpesvirus glycoprotein B inhibits virus replication. J Gen Virol 2004, 85:2131-7.
  • [34]Galdiero S, Falanga A, Vitiello G, Vitiello M, Pedone C, D'Errico G, Galdiero M: Role of membranotropic sequences from herpes simplex virus type I glycoproteins B and H in the fusion process. Biochim Biophys Acta 2010, 1798:579-91.
  • [35]Atanasiu D, Whitbeck JC, de Leon MP, Lou H, Hannah BP, Cohen GH, Eisenberg RJ: Bimolecular complementation defines functional regions of herpes simplex virus gB that are involved with gH/gL as a necessary step leading to cell fusion. J Virol 2010, 84:3825-34.
  • [36]Qian JF, Chen PY, Cai BX: Comparison of growth characteristics between Marek's disease virus and herpesvirus of turkey in chick embryonic cell culture. Chin J Virol 1992, 3:257-261.
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