The Bhella Group

The Bhella Group


Dr David Bhella

  • Programme Leader (Centre for Virus Research)

telephone: 01413303685
email: David.Bhella@glasgow.ac.uk

Research interests

CVR logo

The structural components of viruses represent an intriguing area of study for the structural biologist. In their replication cycle, viruses must generate a protective shell (or capsid) to ferry their genome between hosts. These structural proteins may also be required to facilitate entry to and exit from the host cell, as well as packaging the genome and the necessary functional proteins. In many cases structural proteins are also involved in replication and integration of the viral genome. Thus virus particles are dynamic entities, molecular machines evolved to provide a robust protective shell for the genome and capable of undergoing dramatic conformational changes upon infection of a host cell and in response to specific environmental stimuli.

The fact that many viruses generate their capsids from only one or two protein species makes them all the more remarkable. Viruses attain this level of economy by assembling their capsids in a highly symmetrical manner making these structures not only scientifically interesting but also beautiful.

This group applies the techniques of electron-cryomicroscopy and image analysis to the study of viruses. We are equipped with a high-performance JEOL 2200 cryo-microscope suitable both for high-resolution analysis of symmetrical entities e.g. icosahedral and helical viruses, and for tomographic reconstruction of asymmetrical objects such as enveloped viruses and virus-infected cells. We also have facilities for correlative cryo-fluorescence imaging, high-pressure freezing, automated freeze substitution and cryo-ultramicrotomy. The establishment of these capabilities within a dedicated virus research laboratory gives us an exciting opportunity to visualise the process of virus infection at cellular scale and macromolecular resolution.

We are currently engaged in research into caliciviruses, influenzaviruses and paramyxoviruses (respiratory syncytial virus, parainfluenza viruses and measles virus).

Grants

Grants and Awards listed are those received whilst working with the University of Glasgow.

  • The Scottish Macromolecular Imaging Centre (SMIC)
    Medical Research Council
    2017 - 2022
     
  • Quinquennial Core Funds
    Medical Research Council
    2016 - 2021
     
  • Characterisation of Zika virus neutralisation and virion structure by cryogenic electron microscopy and 3D reconstruction.
    Medical Research Council
    2016 - 2017
     
  • A structure analysis of the intact virion and replicative complexes of human respiratory syncytial virus
    Medical Research Council
    2014 - 2019
     
  • Initiation and regulation of RSV mRNA transcription and genome replication
    National Institute of Allergy and Infectious Diseases
    2014 - 2017
     
  • Structural studies of human viruses and host interactions
    Medical Research Council
    2013 - 2016
     

Publications

List by: Type | Date

Jump to: 2017 | 2016 | 2015 | 2014 | 2013 | 2012 | 2011 | 2010 | 2009 | 2008 | 2007 | 2006 | 2004 | 2003 | 2002 | 2000 | 1999
Number of items: 39.

2017

Burns, A. M. and Bhella, D. (2017) Killer microbes in movies. Microbiology Today, 44(4), pp. 162-165.

Barski, M., Brennan, B., Miller, O. K., Potter, J. A., Vijayakrishnan, S., Bhella, D. , Naismith, J. H., Elliott, R. M. and Schwarz-Linek, U. (2017) Rift Valley fever phlebovirus NSs protein core domain structure suggests molecular basis for nuclear filaments. eLife, 6, e29236. (doi:10.7554/elife.29236) (PMID:28915104) (PMCID:PMC5601994)

Ho, K. L., Kueh, C. L., Beh, P. L., Tan, W. S. and Bhella, D. (2017) Cryo-electron microscopy structure of the Macrobrachium rosenbergii nodavirus capsid at 7 angstroms resolution. Scientific Reports, 7, 2083. (doi:10.1038/s41598-017-02292-0) (PMID:28522842) (PMCID:PMC5437026)

Conley, M., Emmott, E., Orton, R., Taylor, D., Carneiro, D. G., Murata, K., Goodfellow, I. G., Hansman, G. S. and Bhella, D. (2017) Vesivirus 2117 capsids more closely resemble sapovirus and lagovirus particles than other known vesivirus structures. Journal of General Virology, 98(1), pp. 68-76. (doi:10.1099/jgv.0.000658) (PMID:27902397) (PMCID:PMC537039)

2016

Dadonaite, B., Vijayakrishnan, S., Fodor, E., Bhella, D. and Hutchinson, E. C. (2016) Filamentous influenza viruses. Journal of General Virology, 97(8), pp. 1755-1764. (doi:10.1099/jgv.0.000535) (PMID:27365089)

2015

Bhella, D. (2015) The role of cellular adhesion molecules in virus attachment and entry. Philosophical Transactions of the Royal Society B: Biological Sciences, 370(1661), (doi:10.1098/rstb.2014.0035) (PMID:25533093) (PMCID:PMC4275905)

Fan, W. H., Robertson, A. P.E., McElwee, M., Bhella, D., Rixon, F. J. and Lauder, R. (2015) The large tegument protein pUL36 is essential for formation of the capsid vertex-specific component at the capsid-tegument interface of herpes simplex virus 1. Journal of Virology, 89(3), pp. 1502-1511. (doi:10.1128/JVI.02887-14) (PMID:25410861) (PMCID:PMC4300765)

McGonigle, R., Yap, W. B., Ong, S. T., Gatherer, D., Bakker, S. E., Tan, W. S. and Bhella, D. (2015) An N-terminal extension to the hepatitis B virus core protein forms a poorly ordered trimeric spike in assembled virus-like particles. Journal of Structural Biology, 189(2), pp. 73-80. (doi:10.1016/j.jsb.2014.12.006)

2014

Hacker, C., Howell, M., Bhella, D. and Lucocq, J. (2014) Strategies for maximizing ATP supply in the microsporidian Encephalitozoon cuniculi: direct binding of mitochondria to the parasitophorous vacuole and clustering of the mitochondrial porin VDAC. Cellular Microbiology, 16(4), pp. 565-579. (doi:10.1111/cmi.12240) (PMID:24245785) (PMCID:PMC4233961)

2013

Bakker, S. E., Duquerroy, S., Galloux, M., Loney, C., Conner, E., Eleouet, J.-F., Rey, F. A. and Bhella, D. (2013) The respiratory syncytial virus nucleoprotein–RNA complex forms a left-handed helical nucleocapsid. Journal of General Virology, 94(8), pp. 1734-1738. (doi:10.1099/vir.0.053025-0) (PMID:23677789) (PMCID:PMC3749527)

Rihn, S.J., Wilson, S.J., Loman, N.J., Alim, M., Bakker, S.E., Bhella, D., Gifford, R.J., Rixon, F.J. and Bieniasz, P.D. (2013) Extreme genetic fragility of the HIV-1 capsid. PLoS Pathogens, 9(6), e1003461. (doi:10.1371/journal.ppat.1003461) (PMID:23818857) (PMCID:PMC3688543)

Bhella, D. and Bakker, S. E. (2013) Pretty Nasty, symmetry in virus architecture. Biochemist, 35(2), pp. 14-19.

Vijayakrishnan, S., Loney, C., Jackson, D., Suphamungmee, W., Rixon, F.J. and Bhella, D. (2013) Cryotomography of budding influenza a virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end. PLoS Pathogens, 9(6), e1003413. (doi:10.1371/journal.ppat.1003413)

2012

Schmid, M. F., Hecksel, C. W., Rochat, R. H., Bhella, D., Chiu, W. and Rixon, F. J. (2012) A tail-like assembly at the portal vertex in intact herpes simplex type-1 virions. PLoS Pathogens, 8(10), e1002961. (doi:10.1371/journal.ppat.1002961) (PMID:23055933) (PMCID:PMC3464221)

2011

Bhella, D. and Goodfellow, I. G. (2011) The cryo-electron microscopy structure of feline calicivirus bound to junctional adhesion molecule A at 9-angstrom resolution reveals receptor-induced flexibility and two distinct conformational changes in the capsid protein VP1. Journal of Virology, 85(21), pp. 11381-11390. (doi:10.1128/JVI.05621-11) (PMID:21865392) (PMCID:PMC3194967)

Neuman, B. W. et al. (2011) A structural analysis of M protein in coronavirus assembly and morphology. Journal of Structural Biology, 174(1), pp. 11-22. (doi:10.1016/j.jsb.2010.11.021) (PMID:21130884)

2010

Vijayakrishnan, S., Kelly, S.M., Gilbert, R.J.C., Callow, P., Bhella, D., Forsyth, T., Lindsay, J.G. and Byron, O. (2010) Solution structure and characterisation of the human pyruvate dehydrogenase complex core assembly. Journal of Molecular Biology, 399(1), pp. 71-93. (doi:10.1016/j.jmb.2010.03.043) (PMID:20361979) (PMCID:PMC2880790)

Parsons, J.B., Frank, S., Bhella, D., Liang, M., Prentice, M.B., Mulvihill, D.P. and Warren, M.J. (2010) Synthesis of empty bacterial microcompartments, directed organelle protein incorporation, and evidence of filament-associated organelle movement. Molecular Cell, 38(2), pp. 305-315. (doi:10.1016/j.molcel.2010.04.008) (PMID:20417607)

2009

Tawar, R.G. et al. (2009) Crystal structure of a nucleocapsid-like nucleoprotein-RNA complex of respiratory syncytial virus. Science, 326(5957), pp. 1279-1283. (doi:10.1126/science.1177634)

Loney, C., Mottet-Osman, G., Roux, L. and Bhella, D. (2009) Paramyxovirus ultrastructure and genome packaging: cryo-electron tomography of Sendai virus. Journal of Virology, 83(16), pp. 8191-8197. (doi:10.1128/JVI.00693-09)

Alba, R. et al. (2009) Identification of coagulation factor (F)X binding sites on the adenovirus serotype 5 hexon: effect of mutagenesis on FX interactions and gene transfer. Blood, 114(5), pp. 965-971. (doi:10.1182/blood-2009-03-208835)

Greig, J.A. et al. (2009) Influence of Coagulation Factor X on In Vitro and In Vivo Gene Delivery by Adenovirus (Ad) 5, Ad35, and Chimeric Ad5/Ad35 Vectors. Molecular Therapy, 17(10), pp. 1683-1691. (doi:10.1038/mt.2009.152)

2008

Bhella, D., Gatherer, D., Chaudhry, Y., Pink, R. and Goodfellow, I.G. (2008) Structural insights into calicivirus attachment and uncoating. Journal of Virology, 82(16), pp. 8051-8058. (doi:10.1128/JVI.00550-08)

Waddington, S. et al. (2008) Adenovirus serotype 5 hexon mediates liver gene transfer. Cell, 132(3), pp. 397-409. (doi:10.1016/j.cell.2008.01.016)

2007

Maclellan, K., Loney, C., Yeo, R.P. and Bhella, D. (2007) The 24-angstrom structure of respiratory syncytial virus nucleocapsid protein-RNA decameric rings. Journal of Virology, 81(17), pp. 9519-9524. (doi:10.1128/JVI.00526-07)

Tran, T. et al. (2007) The nine C-terminal amino acids of the respiratory syncytial virus protein P are necessary and sufficient for binding to ribonucleoprotein complexes in which six ribonucleotides are contacted per N protein protomer. Journal of General Virology, 88(1), pp. 196-206. (doi:10.1099/vir.0.82282-0)

Bhella, D. (2007) Measles virus nucleocapsid structure, conformational flexibility and the rule of six. In: Longhi, S. (ed.) Measles Virus Nucleoprotein. Series: Intrinsically disordered proteins. Nova Publishers, pp. 37-50. ISBN 9781606925218

Cao, Z., Bhella, D. and Lindsay, J.G. (2007) Reconstitution of the mitochondrial PrxII antioxidant defence pathway: General properties and factors affecting PrxII activity and oligomeric state. Journal of Molecular Biology, 372, pp. 1022-1033. (doi:10.1016/j.jmb.2007.07.018)

Davidson, A.J. and Bhella, D. (2007) Comparative genome and virion structure. In: Arvin, A., Campadelli-Fiume, G. and Mocarski, E. (eds.) Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge University Press. ISBN 9780521827140

2006

Pettigrew, D.M., Williams, D.T., Kerrigan, D., Evans, D.J., Lea, S.M. and Bhella, D. (2006) Structural and functional insights into the interaction of echoviruses and decay-accelerating factor. Journal of Biological Chemistry, 281, pp. 5169-5177. (doi:10.1074/jbc.M510362200)

2004

Bhella, D., Ralph, A. and Yeo, R.P. (2004) Conformational flexibility in recombinant measles virus nucleocapsids visualised by cryo-negative stain electron microscopy and real-space helical reconstruction. Journal of Molecular Biology, 340(2), pp. 319-331. (doi:10.1016/j.jmb.2004.05.015)

Bhella, D., Goodfellow, I.G., Roversi, P., Pettigrew, D., Chaudhry, Y., Evans, D.J. and Lea, S.M. (2004) The structure of echovirus type 12 bound to a two-domain fragment of its cellular attachment protein decay-accelerating factor (CD 55). Journal of Biological Chemistry, 279, pp. 8325-8332. (doi:10.1074/jbc.M311334200)

2003

Longhi, S., Receveur-Bréchot, V., Karlin, D., Johansson, K., Darbon, H., Bhella, D., Yeo, R., Finet, S. and Canard, B. (2003) The C-terminal domain of the measles virus nucleoprotein is intrinsically disordered and folds upon binding to the C-terminal moiety of the phosphoprotein. Journal of Biological Chemistry, 278(20), pp. 18638-18648. (doi:10.1074/jbc.M300518200)

Murphy, L.B., Loney, C., Murray, J., Bhella, D., Ashton, P. and Yeo, R.P. (2003) Investigations into the amino-terminal domain of the respiratory syncytial virus nucleocapsid protein reveal elements important for nucleocapsid formation and interaction with the phosphoprotein. Virology, 307(1), pp. 143-53. (doi:10.1016/S0042-6822(02)00063-6)

2002

Bhella, D., Ralph, A., Murphy, L. and Yeo, R.P. (2002) Significant differences in nucleocapsid morphology within the Paramyxoviridae. Journal of General Virology, 83(8), pp. 1831-1839.

Clayton, R.F., Owsianka, A., Aitken, J., Graham, S., Bhella, D. and Patel, A.H. (2002) Analysis of antigenicity and topology of E2 glycoprotein present on recombinant hepatitis C virus-like particles. Journal of Virology, 76(18), p. 9562. (doi:10.1128/jvi.76.18.9562.2002)

McCLelland, D.A., Aitken, J.D., Bhella, D., McNab, D., Mitchell, J., Kelly, S.M., Price, N.C. and Rixon, F.J. (2002) pH reduction as a trigger for dissociation of herpes simplex virus type 1 scaffolds. Journal of Virology, 76, pp. 7407-7417. (doi:10.1128/VJI.76.15.7407-7417.2002)

2000

Bhella, D., Rixon, F.J. and Dargan, D.J. (2000) Cryomicroscopy of human cytomegalovirus virions reveals more densely packed genomic DNA than in herpes simplex virus type 1. Journal of Molecular Biology, 295(2), pp. 155-161. (doi:10.1006/jmbi.1999.3344)

1999

AL-Khayat, H.A., Bhella, D., Kenney, J.M., Roth, J.F., Kingsman, A.J., Martin-Rendon, E. and Saibil, H.R. (1999) Yeast Ty retrotransposons assemble into virus-like particles whose T-numbers depend on the C-terminal length of the capsid protein. Journal of Molecular Biology, 292(1), pp. 65-73. (doi:10.1006/jmbi.1999.3055)

This list was generated on Mon Jan 22 13:08:57 2018 GMT.
Number of items: 39.

Articles

Burns, A. M. and Bhella, D. (2017) Killer microbes in movies. Microbiology Today, 44(4), pp. 162-165.

Barski, M., Brennan, B., Miller, O. K., Potter, J. A., Vijayakrishnan, S., Bhella, D. , Naismith, J. H., Elliott, R. M. and Schwarz-Linek, U. (2017) Rift Valley fever phlebovirus NSs protein core domain structure suggests molecular basis for nuclear filaments. eLife, 6, e29236. (doi:10.7554/elife.29236) (PMID:28915104) (PMCID:PMC5601994)

Ho, K. L., Kueh, C. L., Beh, P. L., Tan, W. S. and Bhella, D. (2017) Cryo-electron microscopy structure of the Macrobrachium rosenbergii nodavirus capsid at 7 angstroms resolution. Scientific Reports, 7, 2083. (doi:10.1038/s41598-017-02292-0) (PMID:28522842) (PMCID:PMC5437026)

Conley, M., Emmott, E., Orton, R., Taylor, D., Carneiro, D. G., Murata, K., Goodfellow, I. G., Hansman, G. S. and Bhella, D. (2017) Vesivirus 2117 capsids more closely resemble sapovirus and lagovirus particles than other known vesivirus structures. Journal of General Virology, 98(1), pp. 68-76. (doi:10.1099/jgv.0.000658) (PMID:27902397) (PMCID:PMC537039)

Dadonaite, B., Vijayakrishnan, S., Fodor, E., Bhella, D. and Hutchinson, E. C. (2016) Filamentous influenza viruses. Journal of General Virology, 97(8), pp. 1755-1764. (doi:10.1099/jgv.0.000535) (PMID:27365089)

Bhella, D. (2015) The role of cellular adhesion molecules in virus attachment and entry. Philosophical Transactions of the Royal Society B: Biological Sciences, 370(1661), (doi:10.1098/rstb.2014.0035) (PMID:25533093) (PMCID:PMC4275905)

Fan, W. H., Robertson, A. P.E., McElwee, M., Bhella, D., Rixon, F. J. and Lauder, R. (2015) The large tegument protein pUL36 is essential for formation of the capsid vertex-specific component at the capsid-tegument interface of herpes simplex virus 1. Journal of Virology, 89(3), pp. 1502-1511. (doi:10.1128/JVI.02887-14) (PMID:25410861) (PMCID:PMC4300765)

McGonigle, R., Yap, W. B., Ong, S. T., Gatherer, D., Bakker, S. E., Tan, W. S. and Bhella, D. (2015) An N-terminal extension to the hepatitis B virus core protein forms a poorly ordered trimeric spike in assembled virus-like particles. Journal of Structural Biology, 189(2), pp. 73-80. (doi:10.1016/j.jsb.2014.12.006)

Hacker, C., Howell, M., Bhella, D. and Lucocq, J. (2014) Strategies for maximizing ATP supply in the microsporidian Encephalitozoon cuniculi: direct binding of mitochondria to the parasitophorous vacuole and clustering of the mitochondrial porin VDAC. Cellular Microbiology, 16(4), pp. 565-579. (doi:10.1111/cmi.12240) (PMID:24245785) (PMCID:PMC4233961)

Bakker, S. E., Duquerroy, S., Galloux, M., Loney, C., Conner, E., Eleouet, J.-F., Rey, F. A. and Bhella, D. (2013) The respiratory syncytial virus nucleoprotein–RNA complex forms a left-handed helical nucleocapsid. Journal of General Virology, 94(8), pp. 1734-1738. (doi:10.1099/vir.0.053025-0) (PMID:23677789) (PMCID:PMC3749527)

Rihn, S.J., Wilson, S.J., Loman, N.J., Alim, M., Bakker, S.E., Bhella, D., Gifford, R.J., Rixon, F.J. and Bieniasz, P.D. (2013) Extreme genetic fragility of the HIV-1 capsid. PLoS Pathogens, 9(6), e1003461. (doi:10.1371/journal.ppat.1003461) (PMID:23818857) (PMCID:PMC3688543)

Bhella, D. and Bakker, S. E. (2013) Pretty Nasty, symmetry in virus architecture. Biochemist, 35(2), pp. 14-19.

Vijayakrishnan, S., Loney, C., Jackson, D., Suphamungmee, W., Rixon, F.J. and Bhella, D. (2013) Cryotomography of budding influenza a virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end. PLoS Pathogens, 9(6), e1003413. (doi:10.1371/journal.ppat.1003413)

Schmid, M. F., Hecksel, C. W., Rochat, R. H., Bhella, D., Chiu, W. and Rixon, F. J. (2012) A tail-like assembly at the portal vertex in intact herpes simplex type-1 virions. PLoS Pathogens, 8(10), e1002961. (doi:10.1371/journal.ppat.1002961) (PMID:23055933) (PMCID:PMC3464221)

Bhella, D. and Goodfellow, I. G. (2011) The cryo-electron microscopy structure of feline calicivirus bound to junctional adhesion molecule A at 9-angstrom resolution reveals receptor-induced flexibility and two distinct conformational changes in the capsid protein VP1. Journal of Virology, 85(21), pp. 11381-11390. (doi:10.1128/JVI.05621-11) (PMID:21865392) (PMCID:PMC3194967)

Neuman, B. W. et al. (2011) A structural analysis of M protein in coronavirus assembly and morphology. Journal of Structural Biology, 174(1), pp. 11-22. (doi:10.1016/j.jsb.2010.11.021) (PMID:21130884)

Vijayakrishnan, S., Kelly, S.M., Gilbert, R.J.C., Callow, P., Bhella, D., Forsyth, T., Lindsay, J.G. and Byron, O. (2010) Solution structure and characterisation of the human pyruvate dehydrogenase complex core assembly. Journal of Molecular Biology, 399(1), pp. 71-93. (doi:10.1016/j.jmb.2010.03.043) (PMID:20361979) (PMCID:PMC2880790)

Parsons, J.B., Frank, S., Bhella, D., Liang, M., Prentice, M.B., Mulvihill, D.P. and Warren, M.J. (2010) Synthesis of empty bacterial microcompartments, directed organelle protein incorporation, and evidence of filament-associated organelle movement. Molecular Cell, 38(2), pp. 305-315. (doi:10.1016/j.molcel.2010.04.008) (PMID:20417607)

Tawar, R.G. et al. (2009) Crystal structure of a nucleocapsid-like nucleoprotein-RNA complex of respiratory syncytial virus. Science, 326(5957), pp. 1279-1283. (doi:10.1126/science.1177634)

Loney, C., Mottet-Osman, G., Roux, L. and Bhella, D. (2009) Paramyxovirus ultrastructure and genome packaging: cryo-electron tomography of Sendai virus. Journal of Virology, 83(16), pp. 8191-8197. (doi:10.1128/JVI.00693-09)

Alba, R. et al. (2009) Identification of coagulation factor (F)X binding sites on the adenovirus serotype 5 hexon: effect of mutagenesis on FX interactions and gene transfer. Blood, 114(5), pp. 965-971. (doi:10.1182/blood-2009-03-208835)

Greig, J.A. et al. (2009) Influence of Coagulation Factor X on In Vitro and In Vivo Gene Delivery by Adenovirus (Ad) 5, Ad35, and Chimeric Ad5/Ad35 Vectors. Molecular Therapy, 17(10), pp. 1683-1691. (doi:10.1038/mt.2009.152)

Bhella, D., Gatherer, D., Chaudhry, Y., Pink, R. and Goodfellow, I.G. (2008) Structural insights into calicivirus attachment and uncoating. Journal of Virology, 82(16), pp. 8051-8058. (doi:10.1128/JVI.00550-08)

Waddington, S. et al. (2008) Adenovirus serotype 5 hexon mediates liver gene transfer. Cell, 132(3), pp. 397-409. (doi:10.1016/j.cell.2008.01.016)

Maclellan, K., Loney, C., Yeo, R.P. and Bhella, D. (2007) The 24-angstrom structure of respiratory syncytial virus nucleocapsid protein-RNA decameric rings. Journal of Virology, 81(17), pp. 9519-9524. (doi:10.1128/JVI.00526-07)

Tran, T. et al. (2007) The nine C-terminal amino acids of the respiratory syncytial virus protein P are necessary and sufficient for binding to ribonucleoprotein complexes in which six ribonucleotides are contacted per N protein protomer. Journal of General Virology, 88(1), pp. 196-206. (doi:10.1099/vir.0.82282-0)

Cao, Z., Bhella, D. and Lindsay, J.G. (2007) Reconstitution of the mitochondrial PrxII antioxidant defence pathway: General properties and factors affecting PrxII activity and oligomeric state. Journal of Molecular Biology, 372, pp. 1022-1033. (doi:10.1016/j.jmb.2007.07.018)

Pettigrew, D.M., Williams, D.T., Kerrigan, D., Evans, D.J., Lea, S.M. and Bhella, D. (2006) Structural and functional insights into the interaction of echoviruses and decay-accelerating factor. Journal of Biological Chemistry, 281, pp. 5169-5177. (doi:10.1074/jbc.M510362200)

Bhella, D., Ralph, A. and Yeo, R.P. (2004) Conformational flexibility in recombinant measles virus nucleocapsids visualised by cryo-negative stain electron microscopy and real-space helical reconstruction. Journal of Molecular Biology, 340(2), pp. 319-331. (doi:10.1016/j.jmb.2004.05.015)

Bhella, D., Goodfellow, I.G., Roversi, P., Pettigrew, D., Chaudhry, Y., Evans, D.J. and Lea, S.M. (2004) The structure of echovirus type 12 bound to a two-domain fragment of its cellular attachment protein decay-accelerating factor (CD 55). Journal of Biological Chemistry, 279, pp. 8325-8332. (doi:10.1074/jbc.M311334200)

Longhi, S., Receveur-Bréchot, V., Karlin, D., Johansson, K., Darbon, H., Bhella, D., Yeo, R., Finet, S. and Canard, B. (2003) The C-terminal domain of the measles virus nucleoprotein is intrinsically disordered and folds upon binding to the C-terminal moiety of the phosphoprotein. Journal of Biological Chemistry, 278(20), pp. 18638-18648. (doi:10.1074/jbc.M300518200)

Murphy, L.B., Loney, C., Murray, J., Bhella, D., Ashton, P. and Yeo, R.P. (2003) Investigations into the amino-terminal domain of the respiratory syncytial virus nucleocapsid protein reveal elements important for nucleocapsid formation and interaction with the phosphoprotein. Virology, 307(1), pp. 143-53. (doi:10.1016/S0042-6822(02)00063-6)

Bhella, D., Ralph, A., Murphy, L. and Yeo, R.P. (2002) Significant differences in nucleocapsid morphology within the Paramyxoviridae. Journal of General Virology, 83(8), pp. 1831-1839.

Clayton, R.F., Owsianka, A., Aitken, J., Graham, S., Bhella, D. and Patel, A.H. (2002) Analysis of antigenicity and topology of E2 glycoprotein present on recombinant hepatitis C virus-like particles. Journal of Virology, 76(18), p. 9562. (doi:10.1128/jvi.76.18.9562.2002)

McCLelland, D.A., Aitken, J.D., Bhella, D., McNab, D., Mitchell, J., Kelly, S.M., Price, N.C. and Rixon, F.J. (2002) pH reduction as a trigger for dissociation of herpes simplex virus type 1 scaffolds. Journal of Virology, 76, pp. 7407-7417. (doi:10.1128/VJI.76.15.7407-7417.2002)

Bhella, D., Rixon, F.J. and Dargan, D.J. (2000) Cryomicroscopy of human cytomegalovirus virions reveals more densely packed genomic DNA than in herpes simplex virus type 1. Journal of Molecular Biology, 295(2), pp. 155-161. (doi:10.1006/jmbi.1999.3344)

AL-Khayat, H.A., Bhella, D., Kenney, J.M., Roth, J.F., Kingsman, A.J., Martin-Rendon, E. and Saibil, H.R. (1999) Yeast Ty retrotransposons assemble into virus-like particles whose T-numbers depend on the C-terminal length of the capsid protein. Journal of Molecular Biology, 292(1), pp. 65-73. (doi:10.1006/jmbi.1999.3055)

Book Sections

Bhella, D. (2007) Measles virus nucleocapsid structure, conformational flexibility and the rule of six. In: Longhi, S. (ed.) Measles Virus Nucleoprotein. Series: Intrinsically disordered proteins. Nova Publishers, pp. 37-50. ISBN 9781606925218

Davidson, A.J. and Bhella, D. (2007) Comparative genome and virion structure. In: Arvin, A., Campadelli-Fiume, G. and Mocarski, E. (eds.) Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge University Press. ISBN 9780521827140

This list was generated on Mon Jan 22 13:08:57 2018 GMT.

Research group members

Andrew Burns
PhD Student [email]

Research support

Dr Marion McElwee
Research Support

Dr James Streetley
Research Assistant

Dr Swetha Vijaya‌krishnan
Research Associate

Dr Ping Li
Research Fellow

Dr Christopher Syme
Research Associate
   

David Bhella research

Research programme: 

Our group apply the techniques of electron-cryomicroscopy and image analysis to the study of viruses, providing an exciting opportunity to visualise the process of virus infection at cellular scale and at macromolecular resolution.

Current research

Influenza A virus

Influenza A virus tomogramInfluenza A viruses cause seasonal outbreaks of respiratory illness that is often severe. Importantly, new strains frequently emerge to cause pandemics – worldwide epidemics in which many hundreds of millions become infected. We are interested in the structure of these prominent human pathogens; in particular we are studying their propensity to form filamentous virus particles. 

This trait has been postulated to be a feature of wild-type viruses, while laboratory strains more commonly form virions described as being spherical. We have developed novel methods for imaging viruses as they bud from the cell surface, allowing us to analyse the structure of the fragile filaments free of artefacts caused by purification procedures. We found that filaments frequently do not appear to contain genomes at their distal ends, as had been previously assumed, raising questions concerning their role in the infectious process.

Respiratory Syncytial Virus

3D image of Respiratory Syncytial VirusRespiratory syncytial virus (RSV) is an important viral agent of childhood respiratory tract disease worldwide, causing pneumonia and bronchiolitis in infants. We are investigating the structure of the RSV virion and its replicative machinery. Working with partners at the Pasteur Institute and French National Institute for Agricultural Research (Institut National de la Recherche Agronomique – INRA) we recently published an atomic resolution model of the RSV nucleocapsid – a helical structure comprising the viral genome and N protein.

The nucleocapsid, rather than naked viral RNA, is the template for mRNA and genome synthesis, thus understanding its structure is critical in beginning to understand the process of viral replication.

Caliciviruses

Atomic resolution structure of FCV by David BhellaThe calicivirus family includes noroviruses and sapoviruses that cause outbreaks of acute gastroenteritis known as winter vomiting disease. These viruses are particularly challenging to investigate, as they may not be propagated in the laboratory. A tractable surrogate is feline calcivirus, (FCV) a notable veterinary pathogen in its own right that causes respiratory disease in cats. FCV is the only calicivirus for which a protein cellular receptor has been identified – junctional adhesion molecule A (JAM-A).

We are studying the attachment and entry pathway of FCV to build an understanding of the early stages of calicivirus infection. We have published structures of FCV decorated with soluble fragments of JAM-A, revealing conformational changes in the capsid that we propose to be the first stages of uncoating (genome release).

Notable past achievements

Engineering adenoviruses as gene therapy vectors

Adenovirus structureAdenoviruses are widely used as experimental gene therapy vectors as they are capable of delivering a large genetic payload and are able to target a wide range of cell-types. Upon intravenous delivery however, many adenoviruses become coated in the blood coagulation protein Factor X (FX). Coated viruses are then sequestered in the liver.

We solved the structure of adenovirus type 5 decorated with FX, showing that it binds to the major capsid protein known as hexon. By modeling the interaction at atomic resolution we determined a list of key amino-acids on the capsid surface that mediate the interaction. This allowed our colleagues in the Institute of Cardiovascular and Medical Sciences to design mutant viruses that do not bind FX and therefore may be used to target efficiently different organs for gene therapy.

Collaborators

Internal

External

CVR logo