FMDV , G-H loop , insertion sites , FLAG-tagged viruses , reverse genetics," /> FMDV , G-H loop , insertion sites , FLAG-tagged viruses , reverse genetics,"/> FMDV , G-H loop , insertion sites , FLAG-tagged viruses , reverse genetics,"/>
Please wait a minute...
Journal of Integrative Agriculture  2018, Vol. 17 Issue (07): 1655-1666    DOI: 10.1016/S2095-3119(18)61916-1
Animal Science · Veterinary Medicine Advanced Online Publication | Current Issue | Archive | Adv Search |
Insertion site of FLAG on foot-and-mouth disease virus VP1 G-H loop affects immunogenicity of FLAG
ZHU Yuan-yuan1, 2, ZOU Xing-qi2, BAO Hui-fang3, SUN Pu3, MA Xue-qing3, LIU Zai-xin3, FAN Hong-jie1, 4, ZHAO Qi-zu
1 MOE Joint International Research Laboratory of Animal Health and Food Safety/College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, P.R.China
2 China Institute of Veterinary Drug Control, Beijing 100081, P.R.China
3 Lanzhou Veterinary Research Institute, China Academy of Agricultrual Sciences, Lanzhou 730046, P.R.China
4 Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, P.R.China
Download:  PDF (2175KB) ( )  
Export:  BibTeX | EndNote (RIS)      
Abstract  
The G-H loop of the foot-and-mouth disease virus (FMDV) virion contains certain dominant immunogenic epitopes, as well as an arginine-glycine-aspartic acid (RGD) motif that is recognized by cell surface integrin receptors.  Previous experiments indicate that it is critical to maintain virus structural integrity when inserting an exogenous epitope into the surface of an FMDV structural protein.  However, it remains to be determined how factors such as different insertion positions affect interactions among the virus, cells and host immune system.  In this study, one infectious cDNA clone of the swine FMDV Cathay topotype strain O/CHA/90 was constructed.  Then, a FLAG marker (DYKDDDDK) was inserted upstream (–4) or downstream (+10) of the RGD motif to generate tagged viruses vFLAG-O/CHA/90 or vO/CHA/90-FLAG, investigating the possibility of expressing foreign antigen and effect on its immunogenicity.  Compared to the parental virus, both tagged viruses exhibited similar plaque phenotypes, suckling mouse pathogenicity and antigenicity.  Additionally, the FLAG tag insertion position did not change the use of integrin-mediated cell entry by the tagged viruses.  Interestingly, both tagged vaccines protected pigs against challenge with the parental virus O/CHA/90 and induced immune responses against FMDV in BALB/c mice and pigs, but only vaccination with vFLAG-O/CHA/90 generated anti-FLAG antibodies.  Our findings demonstrated that two sites (RGD–4 and RGD+10) tolerated the insertion of an exogenous gene in the swine FMDV O/CHA/90 strain.  However, only RGD–4 was a novel and appropriate inserting site which could tolerate exogenous FLAG.  The resultant tagged virus is a promising candidate for FMD vaccine which can be differentiating infected from vaccinated animals (DIVA).
Keywords:  FMDV ')" href="#">  
Received: 29 November 2017   Accepted:
Fund: This study was supported by the National Key Research and Development Program of China (2016YFD0501500) and the Special Fund for Agro-scientific Research in the Public Interest, China (201303046).
Corresponding Authors:  Correspondence FAN Hong-jie, Tel/Fax: +86-25-84396219, E-mail: fhj@njau.edu.cn; ZHAO Qi-zu, Tel/Fax: +86-10-62103670, E-mail: zhaoqizu@163.com    
About author:  ZHU Yuan-yuan, E-mail: zhuyuanyzz@163.com;
Service
E-mail this article FMDV | G-H loop | insertion sites | FLAG-tagged viruses | reverse genetics”. Please open it by linking:https://www.chinaagrisci.com/Jwk_zgnykxen/EN/abstract/abstract11765.shtml" name="neirong"> FMDV | G-H loop | insertion sites | FLAG-tagged viruses | reverse genetics">
Add to citation manager
E-mail Alert
RSS
Articles by authors
ZHU Yuan-yuan
ZOU Xing-qi
BAO Hui-fang
SUN Pu
MA Xue-qing
LIU Zai-xin
FAN Hong-jie
ZHAO Qi-zu

Cite this article: 

ZHU Yuan-yuan, ZOU Xing-qi, BAO Hui-fang, SUN Pu, MA Xue-qing, LIU Zai-xin, FAN Hong-jie, ZHAO Qi-zu. 2018. Insertion site of FLAG on foot-and-mouth disease virus VP1 G-H loop affects immunogenicity of FLAG. Journal of Integrative Agriculture, 17(07): 1655-1666.

Acharya R, Fry E, Stuart D, Fox G, Rowlands D, Brown F. 1989. The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution. Nature, 337, 709–716.
Alexandersen S, Donaldson A I. 2002. Further studies to quantify the dose of natural aerosols of foot-and-mouth disease virus for pigs. Epidemiology and Infection, 128, 313–323.
Baranowski E, Ruiz-Jarabo C M, Lim F, Domingo E. 2001. Foot-and-mouth disease virus lacking the VP1 G-H loop: The mutant spectrum uncovers interactions among antigenic sites for fitness gain. Virology, 288, 192–202.
Baranowski E, Ruiz-Jarabo C M, Sevilla N, Andreu D, Beck E, Domingo E. 2000. Cell recognition by foot-and-mouth disease virus that lacks the RGD integrin-binding motif: Flexibility in aphthovirus receptor usage. Journal of Virololy, 74, 1641–1647.
Barteling S J, Meloen R H. 1974. A simple method for the quantification of 140S particles of foot-and-mouth disease virus (FMDV). Arch Gesamte Virusforsch, 45, 362–364.
Baxt B, Mason P W. 1995. Foot-and-mouth disease virus undergoes restricted replication in macrophage cell cultures following Fc receptor-mediated adsorption. Virology, 207, 503–509.
Beard C W, Mason P W. 2000. Genetic determinants of altered virulence of Taiwanese foot-and-mouth disease virus. Journal of Virololy, 74, 987–991.
Bittle J L, Houghten R A, Alexander H, Shinnick T M, Sutcliffe J G, Lerner R A, Rowlands D J, Brown F. 1982. Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence. Nature, 298, 30–33.
Burman A, Clark S, Abrescia N G, Fry E E, Stuart D I, Jackson T. 2006. Specificity of the VP1 GH loop of foot-and-mouth disease virus for alpha v integrins. Journal of Virololy, 80, 9798–9810.
Curry S, Fry E, Blakemore W, Abu-Ghazaleh R, Jackson T, King A, Lea S, Newman J, Rowlands D, Stuart D. 1996. Perturbations in the surface structure of A22 Iraq foot-and-mouth disease virus accompanying coupled changes in host cell specificity and antigenicity. Structure, 4, 135–145.
Dicara D, Burman A, Clark S, Berryman S, Howard M J, Hart I R, Marshall J F, Jackson T. 2008. Foot-and-mouth disease virus forms a highly stable, EDTA-resistant complex with its principal receptor, integrin alphavbeta6: Implications for infectiousness. Journal of Virololy, 82, 1537–1546.
Dunn C S, Donaldson A I. 1997. Natural adaption to pigs of a Taiwanese isolate of foot-and-mouth disease virus. Veterinary Record, 141, 174–175.
Fischer D, Rood D, Barrette R W, Zuwallack A, Kramer E, Brown F, Silbart L K. 2003. Intranasal immunization of guinea pigs with an immunodominant foot-and-mouth disease virus peptide conjugate induces mucosal and humoral antibodies and protection against challenge. Journal of Virololy, 77, 7486–7491.
Fry E E, Lea S M, Jackson T, Newman J W, Ellard F M, Blakemore W E, Abu-Ghazaleh R, Samuel A, King A M, Stuart D I. 1999. The structure and function of a foot-and-mouth disease virus-oligosaccharide receptor complex.The Embo Journal, 18, 543–554.
Grell L, Parkin C, Slatest L, Craig P A. 2006. EZ-Viz, a tool for simplifying molecular viewing in PyMOL. Biocheministry of Molecular Biology Education, 34, 402–407.
Grubman M J, Baxt B. 2004. Foot-and-mouth disease. Clinical Microbiology Reviews, 17, 465–493.
Guex N, Peitsch M C. 1997. SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling. Electrophoresis, 18, 2714–2723.
Holinka L G, Fernandez-Sainz I, O’Donnell V, Prarat M V, Gladue D P, Lu Z, Risatti G R, Borca M V. 2009. Development of a live attenuated antigenic marker classical swine fever vaccine. Virology, 384, 106–113.
Jackson T, Ellard F M, Ghazaleh R A, Brookes S M, Blakemore W E, Corteyn A H, Stuart D I, Newman J W, King A M. 1996. Efficient infection of cells in culture by type O foot-and-mouth disease virus requires binding to cell surface heparan sulfate. Journal of Virololy, 70, 5282–5287.
Jackson T, King A M, Stuart D I, Fry E. 2003. Structure and receptor binding. Virus Research, 91, 33–46.
Jackson T, Sharma A, Ghazaleh R A, Blakemore W E, Ellard F M, Simmons D L, Newman J W, Stuart D I, King A M. 1997. Arginine-glycine-aspartic acid-specific binding by foot-and-mouth disease viruses to the purified integrin alpha(v)beta3 in vitro. Journal of Virololy, 71, 8357–8361.
Knowles N J, Davies P R, Henry T, O’Donnell V, Pacheco J M, Mason P W. 2001. Emergence in Asia of foot-and-mouth disease viruses with altered host range: Characterization of alterations in the 3A protein. Journal of Virololy, 75, 1551–1556.
Knowles N J, Samuel A R. 2003. Molecular epidemiology of foot-and-mouth disease virus. Virus Research, 91, 65–80.
Lawrence P, Pacheco J M, Uddowla S, Hollister J, Kotecha A, Fry E, Rieder E. 2013. Foot-and-mouth disease virus (FMDV) with a stable FLAG epitope in the VP1 G-H loop as a new tool for studying FMDV pathogenesis. Virology, 436, 150–161.
Lee S H, Jong M H, Huang T S, Lin Y L, Wong M L, Liu C I, Chang T J. 2009. Pathology and viral distributions of the porcinophilic foot-and-mouth disease virus strain
(O/Taiwan/97) in experimentally infected pigs. Transboundary and Emerging Diseases, 56, 189–201.
Logan D, Abu-Ghazaleh R, Blakemore W, Curry S, Jackson T, King A, Lea S, Lewis R, Newman J, Parry N, Rowlands D, Stuart D, Fry E. 1993. Structure of a major immunogenic site on foot-and-mouth disease virus. Nature, 362, 566–568.
Mahapatra M, Hamblin P, Paton D J. 2012. Foot-and-mouth disease virus epitope dominance in the antibody response of vaccinated animals. Journal of General Virology, 93, 488–493.
Mandl C W, Kroschewski H, Allison S L, Kofler R, Holzmann H, Meixner T, Heinz F X. 2001. Adaptation of tick-borne encephalitis virus to BHK-21 cells results in the formation of multiple heparan sulfate binding sites in the envelope protein and attenuation in vivo. Journal of Virololy, 75, 5627–5637.
Maree F F, Blignaut B, de Beer T A, Visser N, Rieder E A. 2010. Mapping of amino acid residues responsible for adhesion of cell culture-adapted foot-and-mouth disease SAT type viruses. Virus Research, 153, 82–91.
Martinez M A, Hernandez J, Piccone M E, Palma E L, Domingo E, Knowles N, Mateu M G. 1991. Two mechanisms of antigenic diversification of foot-and-mouth disease virus. Virology, 184, 695–706.
Mason P W, Grubman M J, Baxt B. 2003. Molecular basis of pathogenesis of FMDV. Virus Research, 91, 9–32.
Mateu M G, Camarero J A, Giralt E, Andreu D, Domingo E. 1995. Direct evaluation of the immunodominance of a major antigenic site of foot-and-mouth disease virus in a natural host. Virology, 206, 298–306.
McCullough K C, Crowther J R, Carpenter W C, Brocchi E, Capucci L, De Simone F, Xie Q, McCahon D. 1987. Epitopes on foot-and-mouth disease virus particles. I. Topology. Virology, 157, 516–525.
Meloen R H, Briaire J, Woortmeyer R J, van Zaane D. 1983. The main antigenic determinant detected by neutralizing monoclonal antibodies on the intact foot-and-mouth disease virus particle is absent from isolated VPI. Journal of General Virology, 64, 1193–1198.
Neff S, Sa-Carvalho D, Rieder E, Mason P W, Blystone S D, Brown E J, Baxt B. 1998. Foot-and-mouth disease virus virulent for cattle utilizes the integrin alpha(v)beta3 as its receptor. Journal of Virololy, 72, 3587–3594.
OIE (World Organisation for Animal Health). 2016. Chapter 2.1.8. Foot and mouth disease (infection with foot and mouth disease virus). In: Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2016. NB: version adopted in May 2017. http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.01.08_FMD.pdf
Orsel K, de Jong M C, Bouma A, Stegeman J A, Dekker A. 2007. Foot and mouth disease virus transmission among vaccinated pigs after exposure to virus shedding pigs. Vaccine, 25, 6381–6391.
Park M E, Lee S Y, Kim R H, Ko M K, Lee K N, Kim S M, Kim B K, Lee J S, Kim B, Park J H. 2014. Enhanced immune responses of foot-and-mouth disease vaccine using new oil/gel adjuvant mixtures in pigs and goats. Vaccine, 32, 5221–5227.
Parry N, Fox G, Rowlands D, Brown F, Fry E, Acharya R, Logan D, Stuart D. 1990. Structural and serological evidence for a novel mechanism of antigenic variation in foot-and-mouth disease virus. Nature, 347, 569–572.
Rieder E, Baxt B, Lubroth J, Mason P W. 1994. Vaccines prepared from chimeras of foot-and-mouth disease virus (FMDV) induce neutralizing antibodies and protective immunity to multiple serotypes of FMDV. Journal of Virololy, 68, 7092–7098.
Rodriguez L L, Barrera J, Kramer E, Lubroth J, Brown F, Golde W T. 2003. A synthetic peptide containing the consensus sequence of the G-H loop region of foot-and-mouth disease virus type-O VP1 and a promiscuous T-helper epitope induces peptide-specific antibodies but fails to protect cattle against viral challenge. Vaccine, 21, 3751–3756.
Sa-Carvalho D, Rieder E, Baxt B, Rodarte R, Tanuri A, Mason P W. 1997. Tissue culture adaptation of foot-and-mouth disease virus selects viruses that bind to heparin and are attenuated in cattle. Journal of Virololy, 71, 5115–5123.
Salguero F J, Sanchez-Martin M A, Diaz-San Segundo F, de Avila A, Sevilla N. 2005. Foot-and-mouth disease virus (FMDV) causes an acute disease that can be lethal for adult laboratory mice. Virology, 332, 384–396.
Seago J, Jackson T, Doel C, Fry E, Stuart D, Harmsen M M, Charleston B, Juleff N. 2012. Characterization of epitope-tagged foot-and-mouth disease virus. Journal of General Virology, 93, 2371–2381.
Skinner H H. 1951. Propagation of strains of foot-and-mouth disease virus in unweaned white mice. Proceeding of the Royal Society of Medicine, 44, 1041–1044.
Verdaguer N, Schoehn G, Ochoa W F, Fita I, Brookes S, King A, Domingo E, Mateu M G, Stuart D, Hewat E A. 1999. Flexibility of the major antigenic loop of foot-and-mouth disease virus bound to a Fab fragment of a neutralising antibody: Structure and neutralisation. Virology, 255, 260–268.
Wang C Y, Chang T Y, Walfield A M, Ye J, Shen M, Zhang M L, Lubroth J, Chen S P, Li M C, Lin Y L, Jong M H, Yang P C, Chyr N, Kramer E, Brown F. 2001. Synthetic peptide-based vaccine and diagnostic system for effective control of FMD. Biologicals, 29, 221–228.
Wang H, Xue M, Yang D, Zhou G, Wu D, Yu L. 2012. Insertion of type O-conserved neutralizing epitope into the foot-and-mouth disease virus type Asia1 VP1 G-H loop: Effect on viral replication and neutralization phenotype. Journal of General Virology, 93, 1442–1448.
Wang H, Zhao L, Li W, Zhou G, Yu L. 2011. Identification of a conformational epitope on the VP1 G-H Loop of type Asia1 foot-and-mouth disease virus defined by a protective monoclonal antibody. Veterinary Microbiology, 148, 189–199.
Yang B, Yang F, Zhang Y, Liu H, Jin Y, Cao W, Zhu Z, Zheng H, Yin H. 2015. The rescue and evaluation of FLAG and HIS epitope-tagged Asia 1 type foot-and-mouth disease viruses. Virus Research, 213, 246–254.
Yang P C, Chu R M, Chung W B, Sung H T. 1999. Epidemiological characteristics and financial costs of the 1997 foot-and-mouth disease epidemic in Taiwan. Veterinary Record, 145, 731–734.
Zhao Q, Pacheco J M, Mason P W. 2003. Evaluation of genetically engineered derivatives of a Chinese strain of foot-and-mouth disease virus reveals a novel cell-binding site which functions in cell culture and in animals. Journal of Virololy, 77, 3269–3280.
 
No related articles found!
No Suggested Reading articles found!