Structural insights into human bocaparvoviruses

Mario Mietzsch, Shweta Kailasan, Jamie Garrison, Maria Ilyas, Paul Chipman, Kalle Kantola, Mandy E. Janssen, John Spear, Duncan Sousa, Robert McKenna, Kevin Brown, Maria Söderlund-Venermo, Timothy Baker, Mavis Agbandje-McKenna

Research output: Contribution to journalArticlepeer-review

Abstract

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 lifethreatening 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 Å 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.

Original languageEnglish (US)
Article numbere00261-17
JournalJournal of virology
Volume91
Issue number11
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Keywords

  • Capsid
  • Cryo-EM
  • Gastrointestinal infection
  • HBoV
  • Human bocaviruses
  • Parvovirus
  • Respiratory infection

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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