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Structural Insights Into Human Bocaparvoviruses

Title: Structural Insights Into Human Bocaparvoviruses.
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Name(s): Mietzsch, Mario, author
Kailasan, Shweta, author
Garrison, Jamie, author
Ilyas, Maria, author
Chipman, Paul, author
Kantola, Kalle, author
Janssen, Mandy E., author
Spear, John, author
Sousa, Duncan, author
McKenna, Robert, author
Brown, Kevin, author
Soederlund-Venermo, Maria, author
Baker, Timothy, author
Agbandje-McKenna, Mavis, author
Type of Resource: text
Genre: Journal Article
Text
Journal Article
Date Issued: 2017-06
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Bocaparvoviruses are emerging pathogens of the Parvoviridae family. Human bocavirus 1 (HBoV1) causes severe respiratory infections and HBoV2 to HBoV4 cause gastrointestinal infections in young children. Recent reports of life-threatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms highlight the need to study these pathogens on a molecular and structural level for the development of therapeutics. Toward this end, the capsid structures of HBoV1, HBoV3, and HBoV4 were determined to a resolution of 2.8 to 3.0 angstrom by cryo-electron microscopy and three-dimensional image reconstruction. The bocaparvovirus capsids, which display different tissue tropisms, have features in common with other parvoviruses, such as depressions at the icosahedral 2-fold symmetry axis and surrounding the 5-fold symmetry axis, protrusions surrounding the 3-fold symmetry axis, and a channel at the 5-fold symmetry axis. However, unlike other parvoviruses, densities extending the 5-fold channel into the capsid interior are conserved among the bocaparvoviruses and are suggestive of a genus-specific function. Additionally, their major viral protein 3 contains loops with variable regions at their apexes conferring capsid surface topologies different from those of other parvoviruses. Structural comparisons at the strain (HBoV) and genus (bovine parvovirus and HBoV) levels identified differences in surface loops that are functionally important in host/tissue tropism, pathogenicity, and antigenicity in other parvoviruses and likely play similar roles in these viruses. This study thus provides a structural framework to characterize determinants of host/tissue tropism, pathogenicity, and antigenicity for the development of antiviral strategies to control human bocavirus infections. IMPORTANCE Human bocaviruses are one of only a few members of the Parvoviridae family pathogenic to humans, especially young children and immunocompromised adults. There are currently no treatments or vaccines for these viruses or the related enteric bocaviruses. This study obtained the first high-resolution structures of three human bocaparvoviruses determined by cryo-reconstruction. HBoV1 infects the respiratory tract, and HBoV3 and HBoV4 infect the gastrointestinal tract, tissues that are likely targeted by the capsid. Comparison of these viruses provides information on conserved bocaparvovirus-specific features and variable regions resulting in unique surface topologies that can serve as guides to characterize HBoV determinants of tissue tropism and antigenicity in future experiments. Based on the comparison to other existing parvovirus capsid structures, this study suggests capsid regions that likely control successful infection, including determinants of receptor attachment, host cell trafficking, and antigenic reactivity. Overall, these observations could impact efforts to design antiviral strategies and vaccines for HBoVs.
Identifier: FSU_libsubv1_wos_000402166500018 (IID), 10.1128/JVI.00261-17 (DOI)
Keywords: cryoelectron microscopy, adenoassociated virus, capsid, capsid proteins, cryo-EM, frequent detection, gastrointestinal infection, gene-transfer, HBoV, human bocavirus infection, human bocaviruses, parvovirus, parvovirus minute virus, phospholipase-a2 activity, respiratory infection, respiratory-tract infections, type-2 capsids
Publication Note: The publisher's version of record is available at https://doi.org/10.1128/JVI.00261-17
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000402166500018
Owner Institution: FSU
Is Part Of: Journal of Virology.
0022-538X
Issue: iss. 11, vol. 91

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Mietzsch, M., Kailasan, S., Garrison, J., Ilyas, M., Chipman, P., Kantola, K., … Agbandje-McKenna, M. (2017). Structural Insights Into Human Bocaparvoviruses. Journal Of Virology. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000402166500018