Skip to main content

Advertisement

Log in

Cucumber mosaic virus as a presentation system for a double hepatitis C virus-derived epitope

  • Published:
Archives of Virology Aims and scope Submit manuscript

Summary.

Chimeric plant viruses are emerging as promising vectors for use in innovative vaccination strategies. In this context, cucumber mosaic virus (CMV) has proven to be a suitable carrier of the hepatitis C virus (HCV)-derived R9 mimotope. In the present work, a new chimeric CMV, expressing on its surface the HCV-derived R10 mimotope, was produced but lost the insert after the first passage on tobacco. A comparative analysis between R10- and R9-CMV properties indicated that R9-CMV stability was related to structural features typical of the foreign insert. Thus, in order to combine high virus viability with strong immuno-stimulating activity, we doubled R9 copies on each of the 180 coat protein (CP) subunits of CMV. One of the chimeras produced by this approach (2R9-CMV) was shown to systemically infect the host, stably maintaining both inserts. Notably, it was strongly recognized by sera of HCV-infected patients and, as compared with R9-CMV, displayed an enhanced ability to stimulate lymphocyte IFN-γ production. The high immunogen levels achievable in plants or fruits infected with 2R9-CMV suggest that this chimeric form of CMV may be useful in the development of oral vaccines against HCV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • HJD Aizpurua GJ Russell-Jones (1988) ArticleTitleOral vaccination: identification of classes of proteins that provoke an immune response upon oral feeding J Exp Med 167 440–451 10.1084/jem.167.2.440 Occurrence Handle10.1084/jem.167.2.440 Occurrence Handle3346623

    Article  PubMed  Google Scholar 

  • T Arazi PL Huang P Huang L Zhang YM Shiboleth A Gal-On S Lee-Huang (2002) ArticleTitleProduction of antiviral and antitumor proteins MAP30 and GAP31 in cucurbits using the plant virus vector ZYMV-AGII Biochem Biophys Res Commun 292 441–448 10.1006/bbrc.2002.6653 Occurrence Handle10.1006/bbrc.2002.6653 Occurrence Handle1:CAS:528:DC%2BD38XitFeisbc%3D Occurrence Handle11906182

    Article  CAS  PubMed  Google Scholar 

  • RN Beachy JH Fitchen MB Hein (1996) ArticleTitleUse of plant viruses for delivery of vaccine epitopes Ann NY Acad Sci 792 43–49 10.1111/j.1749-6632.1996.tb32489.x Occurrence Handle10.1111/j.1749-6632.1996.tb32489.x Occurrence Handle1:CAS:528:DyaK28XkvVWksrw%3D Occurrence Handle8678419

    Article  CAS  PubMed  Google Scholar 

  • M Bendahamane M Koo E Karrer RN Beachy (1999) ArticleTitleDisplay of epitopes on the surface of tobacco mosaic virus: impact of charge and isoelectric point of the epitope on virus-host interactions J Mol Biol 290 9–20 10.1006/jmbi.1999.2860 Occurrence Handle10.1006/jmbi.1999.2860

    Article  Google Scholar 

  • M Bhasin GPS Raghava (2004) ArticleTitlePrediction of CTL epitopes using QM, SVM and ANN techniques Vaccine 22 3195–3204 10.1016/j.vaccine.2004.02.005 Occurrence Handle10.1016/j.vaccine.2004.02.005 Occurrence Handle1:CAS:528:DC%2BD2cXmsVCqtLw%3D Occurrence Handle15297074

    Article  CAS  PubMed  Google Scholar 

  • FR Brennan T Bellaby SM Helliwell TD Jones S Kamstrup K Dalsgaard JI Flock WDO Hamilton (1999) ArticleTitleChimeric plant virus particles administered nasally or orally induce systemic and mucosal immune responses in mice J Virol 73 IssueID2 930–938 Occurrence Handle1:CAS:528:DyaK1MXmtlWktg%3D%3D Occurrence Handle9882293

    CAS  PubMed  Google Scholar 

  • S Brunak S Buus (2000) ArticleTitleIdentifying cytotoxic T cell epitopes from genomic and proteomic information: “The human MHC project” Rev Immunogenet 2 477–491 Occurrence Handle12361091

    PubMed  Google Scholar 

  • DE Draper (1999) ArticleTitleThemes in RNA-protein recognition J Mol Biol 293 255–270 10.1006/jmbi.1999.2991 Occurrence Handle10.1006/jmbi.1999.2991 Occurrence Handle1:CAS:528:DyaK1MXms12rt7k%3D Occurrence Handle10550207

    Article  CAS  PubMed  Google Scholar 

  • AK El Attar AM Shamloul AA Shalaby BY Riad A Saad HM Mazyad JM Keith (2004) ArticleTitleExpression of chimeric HCV peptide in transgenic tobacco plants infected with recombinant alfalfa mosaic virus for development of a plant derived vaccine against HCV Afr J Biotech 3 588–594 Occurrence Handle1:CAS:528:DC%2BD2MXhslSqs7c%3D

    CAS  Google Scholar 

  • MR Fernàndez-Fernàndez JL Martinez-Torrecuadrada JI Casal JA Garcia (1998) ArticleTitleDevelopment of an antigen presentation system based on plum pox potyvirus FEBS Lett 427 229–235 10.1016/S0014-5793(98)00429-3 Occurrence Handle10.1016/S0014-5793(98)00429-3 Occurrence Handle9607317

    Article  PubMed  Google Scholar 

  • MJ Francis (1990) ArticleTitlePeptide vaccines for viral diseases Sci Progr 74 115–130 Occurrence Handle1:STN:280:DyaK3M%2FpsF2ltg%3D%3D

    CAS  Google Scholar 

  • L Frasca C Scottà P Del Porto A Nicosia C Pasquazzi I Versace AM Masci L Racioppi E Piccolella (2003) ArticleTitleAntibody-selected mimics of hepatitis C virus hypervariable region 1 activate both primary and memory Th lymphocytes Hepatology 38 653–662 10.1053/jhep.2003.50387 Occurrence Handle10.1053/jhep.2003.50387 Occurrence Handle1:CAS:528:DC%2BD3sXnvVKjt7g%3D Occurrence Handle12939592

    Article  CAS  PubMed  Google Scholar 

  • A Gellért K Salánki G Náray-Szabó E Balázs (2006) ArticleTitleHomology modelling and protein structure based functional analysis of five cucumovirus coat proteins J Mol Graph Model 24 319–327 10.1016/j.jmgm.2005.09.015 Occurrence Handle10.1016/j.jmgm.2005.09.015 Occurrence Handle16257549

    Article  PubMed  Google Scholar 

  • N Guex MC Peitsch (1997) ArticleTitleSWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modelling Electrophoresis 18 2714–2723 10.1002/elps.1150181505 Occurrence Handle10.1002/elps.1150181505 Occurrence Handle1:CAS:528:DyaK1cXhvFaks70%3D Occurrence Handle9504803

    Article  CAS  PubMed  Google Scholar 

  • T Joelson L Akerblom P Oxelfelt B Strandberg K Tomenius TJ Morris (1997) ArticleTitlePresentation of a foreign peptide on the surface of tomato bushy stunt virus J Gen Virol 78 1213–1217 Occurrence Handle1:CAS:528:DyaK2sXjslamsb8%3D Occurrence Handle9191910

    CAS  PubMed  Google Scholar 

  • J Johnson T Lin G Lomonossoff (1997) ArticleTitlePresentation of heterologous peptides on plant viruses: genetics, structure, and function Annu Rev Phytophathol 35 67–86 10.1146/annurev.phyto.35.1.67 Occurrence Handle10.1146/annurev.phyto.35.1.67 Occurrence Handle1:CAS:528:DyaK2sXmtVGiu7Y%3D

    Article  CAS  Google Scholar 

  • DG Kneller FE Cohen R Langridge (1990) ArticleTitleImprovements in protein secondary structure prediction by an enhanced neural network J Mol Biol 214 171–182 10.1016/0022-2836(90)90154-E Occurrence Handle10.1016/0022-2836(90)90154-E Occurrence Handle1:CAS:528:DyaK3cXkvFCgtr4%3D Occurrence Handle2370661

    Article  CAS  PubMed  Google Scholar 

  • R Konecny J Trylska F Tama D Zhang NA Baker CL Brooks JA McCammon (2005) ArticleTitleElectrostatic properties of cowpea chlorotic mottle virus and cucumber mosaic virus capsids Biopolymers 82 106–120 10.1002/bip.20409 Occurrence Handle10.1002/bip.20409

    Article  Google Scholar 

  • M Koo M Bendahmane GA Lettieri AD Paoletti TE Lane JH Fitchen MJ Buchmeier RN Beachy (1999) ArticleTitleProtective immunity against murine hepatitis virus (MHV) induced by intranasal or subcutaneous administration of hybrids of tobacco mosaic virus that carries an MHV epitope Proc Natl Acad Sci USA 96 7774–7779 10.1073/pnas.96.14.7774 Occurrence Handle10.1073/pnas.96.14.7774 Occurrence Handle1:CAS:528:DyaK1MXltVOkt7o%3D Occurrence Handle10393897

    Article  CAS  PubMed  Google Scholar 

  • H Lot J Marrou JB Quiot C Esvan (1972) ArticleTitleContribution à l’étude du virus de la mosaique du cocombre (CMV). I. Mèthode de purification rapide du virus Ann Phytopathol 14 25–38

    Google Scholar 

  • C Marusic P Rizza L Lattanzi C Mancini M Spada F Belardelli E Benvenuto I Capone (2001) ArticleTitleChimeric plant virus particles as immunogens for inducing murine and human immune responses against human immunodeficiency virus type1 J Virol 75 8434–8439 10.1128/JVI.75.18.8434-8439.2001 Occurrence Handle10.1128/JVI.75.18.8434-8439.2001 Occurrence Handle1:CAS:528:DC%2BD3MXmsVarurk%3D Occurrence Handle11507188

    Article  CAS  PubMed  Google Scholar 

  • L McLain Z Durrani LA Wisniewski C Porta GP Lomonossoff NJ Dimmock (1996) ArticleTitleStimulation of neutralizing antibodies to human immunodeficiency virus type 1 in three strains of mice immunized with a 22 amino acid peptide of gp41 expressed on the surface of a plant virus Vaccine 14 799–810 10.1016/0264-410X(95)00229-T Occurrence Handle10.1016/0264-410X(95)00229-T Occurrence Handle1:CAS:528:DyaK28XkvV2gtL4%3D Occurrence Handle8817828

    Article  CAS  PubMed  Google Scholar 

  • ML Memon MA Memon (2002) ArticleTitleHepatitis C: an epidemiological review J Viral Hepatol 9 84–100 10.1046/j.1365-2893.2002.00329.x Occurrence Handle10.1046/j.1365-2893.2002.00329.x Occurrence Handle1:STN:280:DC%2BD383ktFGrtw%3D%3D

    Article  CAS  Google Scholar 

  • A Natilla G Piazzolla M Nuzzaci P Saldarelli C Tortorella S Antonaci P Piazzolla (2004) ArticleTitleCucumber mosaic virus as a carrier of a hepatitis C virus-derived epitope Arch Virol 149 137–154 10.1007/s00705-003-0190-x Occurrence Handle10.1007/s00705-003-0190-x Occurrence Handle1:CAS:528:DC%2BD3sXpvVKqtrk%3D Occurrence Handle14689280

    Article  CAS  PubMed  Google Scholar 

  • A Natilla RW Hammond LG Nemchinov (2006) ArticleTitleEpitope presentation system based on cucumber mosaic virus coat protein expressed from a potato virus X-based vector Arch Virol 151 IssueID7 1373–1386 10.1007/s00705-005-0711-x Occurrence Handle10.1007/s00705-005-0711-x Occurrence Handle1:CAS:528:DC%2BD28XmtFGqur8%3D Occurrence Handle16489509

    Article  CAS  PubMed  Google Scholar 

  • LG Nemchinov TJ Liang MM Rifaat HM Mazyad A Hadidi JM Keith (2000) ArticleTitleDevelopment of a plant-derived subunit vaccine candidate against hepatitis C virus Arch Virol 145 2557–2573 10.1007/s007050070008 Occurrence Handle10.1007/s007050070008 Occurrence Handle1:CAS:528:DC%2BD3MXhtFCjsbw%3D Occurrence Handle11205105

    Article  CAS  PubMed  Google Scholar 

  • BL Nicholas FR Brennan JL Martinez-Torrecuadrada JI Casal WD Hamilton D Wakelin (2002) ArticleTitleCharacterization of the immune response to canine parvovirus induced by vaccination with chimaeric plant viruses Vaccine 20 2727–2734 10.1016/S0264-410X(02)00200-1 Occurrence Handle10.1016/S0264-410X(02)00200-1 Occurrence Handle1:CAS:528:DC%2BD38XktVCrtb0%3D Occurrence Handle12034099

    Article  CAS  PubMed  Google Scholar 

  • LF Pacios F Garcia-Arenal (2006) ArticleTitleComparison of properties of particles of cucumber mosaic virus and Tomato aspermy virus based on the analysis of molecular surfaces of capsids J Gen Virol 87 2073–2083 10.1099/vir.0.81621-0 Occurrence Handle10.1099/vir.0.81621-0 Occurrence Handle1:CAS:528:DC%2BD28Xms1Clurg%3D Occurrence Handle16760411

    Article  CAS  PubMed  Google Scholar 

  • KL Perry L Zhang MH Shintaku P Palukaitis (1994) ArticleTitleMapping determinants in cucumber mosaic virus for transmission by Aphis gossypii Virology 205 591–595 10.1006/viro.1994.1686 Occurrence Handle10.1006/viro.1994.1686 Occurrence Handle1:CAS:528:DyaK2MXit12qu7w%3D Occurrence Handle7975263

    Article  CAS  PubMed  Google Scholar 

  • G Piazzolla M Nuzzaci C Tortorella E Panella A Natilla D Boscia A De Stradis P Piazzolla S Antonaci (2005) ArticleTitleImmunogenic properties of a chimeric plant virus expressing a hepatitis C virus (HCV)-derived epitope: new prospects for an HCV vaccine J Clin Immunal 25 142–152 10.1007/s10875-005-2820-4 Occurrence Handle10.1007/s10875-005-2820-4 Occurrence Handle1:CAS:528:DC%2BD2MXjtFehtb4%3D

    Article  CAS  Google Scholar 

  • C Porta VE Spall J Loveland JE Johnson PJ Barker (1994) ArticleTitleDevelopment of cowpea mosaic virus as a high-yielding system for the presentation of foreign peptides Virology 202 949–955 10.1006/viro.1994.1417 Occurrence Handle10.1006/viro.1994.1417 Occurrence Handle1:CAS:528:DyaK2cXlsV2qtLY%3D Occurrence Handle8030255

    Article  CAS  PubMed  Google Scholar 

  • C Porta VE Spall KC Findlay RS Gergerich CE Farrance G Lomonossoff (2003) ArticleTitleCowpea mosaic virus-based chimaeras. Effects of inserted peptides on the phenotype, host range, and transmissibility of the modified virus Virology 310 50–63 10.1016/S0042-6822(03)00140-5 Occurrence Handle10.1016/S0042-6822(03)00140-5 Occurrence Handle1:CAS:528:DC%2BD3sXkt1yjt70%3D Occurrence Handle12788630

    Article  CAS  PubMed  Google Scholar 

  • G Puntoriero A Meola A Lahm S Zucchelli B Bruni-Ercole R Tafi M Pezzanera MU Mondelli R Cortese A Tramontano G Galfre’ A Nicosia (1998) ArticleTitleToward a solution for hepatitis C virus hypervariability: mimotopes of the hypervariable region 1 can induce antibodies cross-reacting with a large number of viral variants EMBO J 13 3521–3533 10.1093/emboj/17.13.3521 Occurrence Handle10.1093/emboj/17.13.3521

    Article  Google Scholar 

  • LJ Richter Y Thanavala CJ Arntzen HS Mason (2000) ArticleTitleProduction of hepatitis B surface antigen in transgenic plants for oral immunization Nat Biotechnol 18 1167–1171 10.1038/81153 Occurrence Handle10.1038/81153 Occurrence Handle1:CAS:528:DC%2BD3cXotVSmu78%3D Occurrence Handle11062435

    Article  CAS  PubMed  Google Scholar 

  • S Rosemberg (2001) ArticleTitleRecent advances in the molecular biology of hepatitis C virus J Mol Biol 313 451–464 10.1006/jmbi.2001.5055 Occurrence Handle10.1006/jmbi.2001.5055

    Article  Google Scholar 

  • J Sambrook DW Russell (2001) Molecular cloning: a laboratory manual Cold Spring Harbor Laboratory Press Cold Spring Harbor, New York

    Google Scholar 

  • PJ Scheuer (1991) ArticleTitleClassification of chronic viral hepatitis: a need for reassessment J Hepatol 13 372–374 10.1016/0168-8278(91)90084-O Occurrence Handle10.1016/0168-8278(91)90084-O Occurrence Handle1:STN:280:DyaK383is1CrtQ%3D%3D Occurrence Handle1808228

    Article  CAS  PubMed  Google Scholar 

  • TJ Smith E Chase T Schmidt KL Perry (2000) ArticleTitleThe structure of cucumber mosaic virus and comparison to cowpea chlorotic mottle virus J Virol 74 7578–7686 10.1128/JVI.74.16.7578-7586.2000 Occurrence Handle10.1128/JVI.74.16.7578-7586.2000 Occurrence Handle1:CAS:528:DC%2BD3cXlt1Grsb4%3D Occurrence Handle10906212

    Article  CAS  PubMed  Google Scholar 

  • CO Tacket HS Mason (1999) ArticleTitleA review of oral vaccination with transgenic vegetables Microbes Infect 1 777–783 10.1016/S1286-4579(99)80080-X Occurrence Handle10.1016/S1286-4579(99)80080-X Occurrence Handle1:STN:280:DC%2BD3c3ntlGqtw%3D%3D Occurrence Handle10816083

    Article  CAS  PubMed  Google Scholar 

  • CO Tacket MB Sztein GA Losonsky SS Wasserman MK Estes (2003) ArticleTitleHumoral, mucosal, and cellular immune responses to oral Norwalk virus-like particles in volunteers Clin Immunol 108 241–247 10.1016/S1521-6616(03)00120-7 Occurrence Handle10.1016/S1521-6616(03)00120-7 Occurrence Handle1:CAS:528:DC%2BD3sXnt1ynt7c%3D Occurrence Handle14499247

    Article  CAS  PubMed  Google Scholar 

  • N Takamatsu Y Watanabe H Yanagi T Meshi T Shiba Y Okada (1990) ArticleTitleProduction of enkephalin in tobacco protoplasts using tobacco mosaic virus RNA vector FEBS Lett 269 73–76 10.1016/0014-5793(90)81121-4 Occurrence Handle10.1016/0014-5793(90)81121-4 Occurrence Handle1:CAS:528:DyaK3cXls1Kkur4%3D Occurrence Handle2387417

    Article  CAS  PubMed  Google Scholar 

  • Y Thanavala M Mahoney S Pal A Scott L Richter N Natarajan P Goodwin CJ Arntzen HS Mason (2005) ArticleTitleImmunogenicity in humans of an edible vaccine for hepatitis B Proc Natl Acad Sci USA 102 IssueID9 3378–3382 10.1073/pnas.0409899102 Occurrence Handle10.1073/pnas.0409899102 Occurrence Handle1:CAS:528:DC%2BD2MXitl2luro%3D Occurrence Handle15728371

    Article  CAS  PubMed  Google Scholar 

  • TH Turpen SJ Reini Y Charoenvit SL Hoffman V Fallarme LK Grill (1995) ArticleTitleMalarial epitopes expressed on the surface of recombinant tobacco mosaic virus Biotechnology 13 53–57 10.1038/nbt0195-53 Occurrence Handle10.1038/nbt0195-53 Occurrence Handle1:CAS:528:DyaK2MXivFOgsL4%3D Occurrence Handle9634749

    Article  CAS  PubMed  Google Scholar 

  • A Wasley MJ Alter (2000) ArticleTitleEpidemiology of hepatitis C: geographic differences and temporal trends Semin Liver Dis 20 1–16 10.1055/s-2000-9506 Occurrence Handle10.1055/s-2000-9506 Occurrence Handle1:STN:280:DC%2BD3M%2Fit12ltg%3D%3D Occurrence Handle10895428

    Article  CAS  PubMed  Google Scholar 

  • WR Wikoff CJ Tsai G Wang TS Baker JE Johnson (1997) ArticleTitleThe structure of cucumber mosaic virus: cryoelectron microscopy, X-ray crystallography, and sequence analysis Virology 232 91–97 10.1006/viro.1997.8543 Occurrence Handle10.1006/viro.1997.8543 Occurrence Handle1:CAS:528:DyaK2sXjsFaqt7Y%3D Occurrence Handle9185592

    Article  CAS  PubMed  Google Scholar 

  • V Yusibov DC Hooper SV Spitsin N Fleysh RB Kean T Mikheeva D Deka A Karasev S Cox J Randall H Koprowski (2002) ArticleTitleExpression in plants and immunogenicity of plant virus-based experimental rabies vaccine Vaccine 20 3155–3164 10.1016/S0264-410X(02)00260-8 Occurrence Handle10.1016/S0264-410X(02)00260-8 Occurrence Handle1:CAS:528:DC%2BD38XmtVSrtbk%3D Occurrence Handle12163267

    Article  CAS  PubMed  Google Scholar 

  • Y Zhao RW Hammond (2005) ArticleTitleDevelopment of a candidate vaccine for newcastle disease virus by epitope display in the cucumber mosaic virus capsid protein Biotechnol Lett 27 375–382 10.1007/s10529-005-1773-2 Occurrence Handle10.1007/s10529-005-1773-2 Occurrence Handle1:CAS:528:DC%2BD2MXjtlKmu7g%3D Occurrence Handle15834801

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nuzzaci, M., Piazzolla, G., Vitti, A. et al. Cucumber mosaic virus as a presentation system for a double hepatitis C virus-derived epitope. Arch Virol 152, 915–928 (2007). https://doi.org/10.1007/s00705-006-0916-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-006-0916-7

Keywords

Navigation