This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Walters, R. W.
Right arrow Articles by Zabner, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Walters, R. W.
Right arrow Articles by Zabner, J.

 Previous Article  |  Next Article 

Journal of Virology, April 2004, p. 3361-3371, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3361-3371.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Structure of Adeno-Associated Virus Serotype 5

Robert W. Walters,1,2,{dagger} Mavis Agbandje-McKenna,3,{dagger} Valorie D. Bowman,4,{dagger} Thomas O. Moninger,1 Norman H. Olson,4 Michael Seiler,1 John A. Chiorini,5 Timothy S. Baker,4 and Joseph Zabner1*

Departments of Internal Medicine,1 Physiology and Biophysics, College of Medicine, University of Iowa, Iowa City, Iowa 52242,2 Department of Biochemistry and Molecular Biology, Center for Structural Biology, The Brain Institute, University of Florida College of Medicine, Gainesville, Florida 32610,3 Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907,4 Gene Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 208925

Received 2 September 2003/ Accepted 4 December 2003

Adeno-associated virus serotype 5 (AAV5) requires sialic acid on host cells to bind and infect. Other parvoviruses, including Aleutian mink disease parvovirus (ADV), canine parvovirus (CPV), minute virus of mice, and bovine parvovirus, also bind sialic acid. Hence, structural homology may explain this functional homology. The amino acids required for CPV sialic acid binding map to a site at the icosahedral twofold axes of the capsid. In contrast to AAV5, AAV2 does not bind sialic acid, but rather binds heparan sulfate proteoglycans at its threefold axes of symmetry. To explore the structure-function relationships among parvoviruses with respect to cell receptor attachment, we determined the structure of AAV5 by cryo-electron microscopy (cryo-EM) and image reconstruction at a resolution of 16 Å. Surface features common to some parvoviruses, namely depressions encircling the fivefold axes and protrusions at or surrounding the threefold axes, are preserved in the AAV5 capsid. However, even though there were some similarities, a comparison of the AAV5 structure with those of ADV and CPV failed to reveal a feature which could account for the sialic acid binding phenotype common to all three viruses. In contrast, the overall surface topologies of AAV5 and AAV2 are similar. A pseudo-atomic model generated for AAV5 based on the crystal structure of AAV2 and constrained by the AAV5 cryo-EM envelope revealed differences only in surface loop regions. Surprisingly, the surface topologies of AAV5 and AAV2 are remarkably similar to that of ADV despite only exhibiting ~20% identity in amino acid sequences. Thus, capsid surface features are shared among parvoviruses and may not be unique to their replication phenotypes, i.e., whether they require a helper or are autonomous. Furthermore, specific surface features alone do not explain the variability in carbohydrate requirements for host cell receptor interactions among parvoviruses.

* Corresponding author. Mailing address: University of Iowa College of Medicine, 500 EMRB, Iowa City, IA 52242. Phone: (319) 353-5511. Fax: (319) 335-7623. E-mail: joseph-zabner{at}uiowa.edu.

{dagger} R.W.W., M.A.-M., and V.D.B. contributed equally to this work.

Journal of Virology, April 2004, p. 3361-3371, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3361-3371.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mays, L. E., Vandenberghe, L. H., Xiao, R., Bell, P., Nam, H.-J., Agbandje-McKenna, M., Wilson, J. M. (2009). Adeno-Associated Virus Capsid Structure Drives CD4-Dependent CD8+ T Cell Response to Vector Encoded Proteins. J. Immunol. 182: 6051-6060 [Abstract] [Full Text]  
  • Excoffon, K. J. D. A., Koerber, J. T., Dickey, D. D., Murtha, M., Keshavjee, S., Kaspar, B. K., Zabner, J., Schaffer, D. V. (2009). Directed evolution of adeno-associated virus to an infectious respiratory virus. Proc. Natl. Acad. Sci. USA 106: 3865-3870 [Abstract] [Full Text]  
  • DiPrimio, N., Asokan, A., Govindasamy, L., Agbandje-McKenna, M., Samulski, R. J. (2008). Surface Loop Dynamics in Adeno-Associated Virus Capsid Assembly. J. Virol. 82: 5178-5189 [Abstract] [Full Text]  
  • Nam, H.-J., Lane, M. D., Padron, E., Gurda, B., McKenna, R., Kohlbrenner, E., Aslanidi, G., Byrne, B., Muzyczka, N., Zolotukhin, S., Agbandje-McKenna, M. (2007). Structure of Adeno-Associated Virus Serotype 8, a Gene Therapy Vector. J. Virol. 81: 12260-12271 [Abstract] [Full Text]  
  • Grieger, J. C., Johnson, J. S., Gurda-Whitaker, B., Agbandje-McKenna, M., Samulski, R. J. (2007). Surface-Exposed Adeno-Associated Virus Vp1-NLS Capsid Fusion Protein Rescues Infectivity of Noninfectious Wild-Type Vp2/Vp3 and Vp3-Only Capsids but Not That of Fivefold Pore Mutant Virions. J. Virol. 81: 7833-7843 [Abstract] [Full Text]  
  • Govindasamy, L., Padron, E., McKenna, R., Muzyczka, N., Kaludov, N., Chiorini, J. A., Agbandje-McKenna, M. (2006). Structurally Mapping the Diverse Phenotype of Adeno-Associated Virus Serotype 4. J. Virol. 80: 11556-11570 [Abstract] [Full Text]  
  • Wu, Z., Miller, E., Agbandje-McKenna, M., Samulski, R. J. (2006). {alpha}2,3 and {alpha}2,6 N-Linked Sialic Acids Facilitate Efficient Binding and Transduction by Adeno-Associated Virus Types 1 and 6.. J. Virol. 80: 9093-9103 [Abstract] [Full Text]  
  • Besselsen, D. G., Romero, M. J., Wagner, A. M., Henderson, K. S., Livingston, R. S. (2006). Identification of novel murine parvovirus strains by epidemiological analysis of naturally infected mice. J. Gen. Virol. 87: 1543-1556 [Abstract] [Full Text]  
  • Lopez-Bueno, A., Rubio, M.-P., Bryant, N., McKenna, R., Agbandje-McKenna, M., Almendral, J. M. (2006). Host-Selected Amino Acid Changes at the Sialic Acid Binding Pocket of the Parvovirus Capsid Modulate Cell Binding Affinity and Determine Virulence. J. Virol. 80: 1563-1573 [Abstract] [Full Text]  
  • Kontou, M., Govindasamy, L., Nam, H.-J., Bryant, N., Llamas-Saiz, A. L., Foces-Foces, C., Hernando, E., Rubio, M.-P., McKenna, R., Almendral, J. M., Agbandje-McKenna, M. (2005). Structural Determinants of Tissue Tropism and In Vivo Pathogenicity for the Parvovirus Minute Virus of Mice. J. Virol. 79: 10931-10943 [Abstract] [Full Text]  
  • Grieger, J. C., Samulski, R. J. (2005). Packaging Capacity of Adeno-Associated Virus Serotypes: Impact of Larger Genomes on Infectivity and Postentry Steps. J. Virol. 79: 9933-9944 [Abstract] [Full Text]  
  • Padron, E., Bowman, V., Kaludov, N., Govindasamy, L., Levy, H., Nick, P., McKenna, R., Muzyczka, N., Chiorini, J. A., Baker, T. S., Agbandje-McKenna, M. (2005). Structure of Adeno-Associated Virus Type 4. J. Virol. 79: 5047-5058 [Abstract] [Full Text]  
  • Bleker, S., Sonntag, F., Kleinschmidt, J. A. (2005). Mutational Analysis of Narrow Pores at the Fivefold Symmetry Axes of Adeno-Associated Virus Type 2 Capsids Reveals a Dual Role in Genome Packaging and Activation of Phospholipase A2 Activity. J. Virol. 79: 2528-2540 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»