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Publication Abstract from PubMed

Bocaparvoviruses are emerging pathogens of the Parvoviridae family. Human bocaviruses 1 (HBoV1) causes severe respiratory infections and HBoV2-4 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 demand the need to study these pathogens on a molecular and structural level for the development of therapeutics. Towards this end, the capsid structures of HBoV1, HBoV3, and HBoV4 were determined to 2.8 - 3.0 A resolution using cryo-electron microscopy and 3D image reconstruction. The bocaparvovirus capsids, that display different tissue tropisms, share common features with other parvoviruses, such as depressions at the icosahedral 2-fold and surrounding the 5-fold symmetry axes, protrusions surrounding the 3-fold, and a channel at the 5-fold axis. However, unlike other parvoviruses densities extending the 5-fold channel into the capsid interior are conserved among the bocaparvoviruses and are suggestive of genus specific function. Additionally, their major viral protein 3 contains loops with variable regions at their apexes conferring unique capsid surface topologies relative to other parvoviruses. Structural comparisons at strain (HBoVs) and genus (bovine parvovirus and HBoVs) levels identified differences in surface loops functionally important in host/tissue tropism, pathogenicity, and antigenicity in other parvoviruses, and likely play similar roles for these viruses. This study thus provides a structural framework to characterize determinants of host/tissue tropism, pathogenicity, and antigenicity for the development of anti-viral 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 reports the first high-resolution structures of three human bocaparvoviruses determined by cryo-reconstruction. HBoV1 infects the respiratory tract, HBoV3 and HBoV4 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. When compared to other existing parvovirus capsid structures this study suggests capsid regions that likely control successful infection, including determinants for receptor attachment, host cell trafficking, and antigenic reactivity. Overall these observations could impact efforts to design anti-viral strategies and vaccines for the HBoVs.

Structural insights into emerging pediatric pathogens human bocaparvoviruses.,Mietzsch M, Kailasan S, Garrison J, Ilyas M, Chipman P, Kantola K, Janssen ME, Spear J, Sousa D, McKenna R, Brown K, Soderlund-Venermo M, Baker T, Agbandje-McKenna M J Virol. 2017 Mar 22. pii: JVI.00261-17. doi: 10.1128/JVI.00261-17. PMID:28331084^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.