Structural Characterization of Cuta- and Tusavirus: Insight into Protoparvoviruses Capsid Morphology

Mario Mietzsch,J Kennon Smith,Maria Ilyas,David Smith,Paul Chipman,Joshua A Hull,Maria Söderlund-Venermo,Jennifer C Yu,Elina Väisänen,Yi Lasanajak,Robert Mckenna,Mavis Agbandje-Mckenna,Justin Kurian

doi:10.3390/v12060653

Mario Mietzsch, J Kennon Smith + Show 11 more

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https://doi.org/10.3390/v12060653

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Abstract

Several members of the Protoparvovirus genus, capable of infecting humans, have been recently discovered, including cutavirus (CuV) and tusavirus (TuV). To begin the characterization of these viruses, we have used cryo-electron microscopy and image reconstruction to determine their capsid structures to ~2.9 Å resolution, and glycan array and cell-based assays to identify glycans utilized for cellular entry. Structural comparisons show that the CuV and TuV capsids share common features with other parvoviruses, including an eight-stranded anti-parallel β-barrel, depressions at the icosahedral 2-fold and surrounding the 5-fold axes, and a channel at the 5-fold axes. However, the viruses exhibit significant topological differences in their viral protein surface loops. These result in three separated 3-fold protrusions, similar to the bufaviruses also infecting humans, suggesting a host-driven structure evolution. The surface loops contain residues involved in receptor binding, cellular trafficking, and antigenic reactivity in other parvoviruses. In addition, terminal sialic acid was identified as the glycan potentially utilized by both CuV and TuV for cellular entry, with TuV showing additional recognition of poly-sialic acid and sialylated Lewis X (sLeXLeXLeX) motifs reported to be upregulated in neurotropic and cancer cells, respectively. These structures provide a platform for annotating the cellular interactions of these human pathogens.

Highlights

The members of the Parvoviridae are linear, non-segmented, single-stranded DNA viruses, with a genome of ~4–6 kb [1]
Because of these new “variabilities” compared to the structurally conserved regions we propose a new assignment of the protoparvovirus variable regions (VRs) (Figure 3, blue VR numbering) following numerical order that is more comparable to the VRs of the dependo- and bocaparvoviruses [6]
This study reports the capsid structures for two of the most divergent viruses so far discovered in the Protoparvovirus genus

Summary

Introduction

The members of the Parvoviridae are linear, non-segmented, single-stranded DNA viruses, with a genome of ~4–6 kb [1]. Parvoviruses are among the smallest viruses ( the name, from the Latin word parvus meaning small) with a non-enveloped capsid of 215–260 Å in diameter. They infect a wide range of hosts, reflected by the three subfamilies: the members of the Parvovirinae infect vertebrates, those of the Densovirinae infect arthropods, and those of the Hamaparvovirinae infect either vertebrates or invertebrates [1,2]. Five of the ten genera in this subfamily contain viruses capable of infecting humans: Bocaparvovirus (e.g., human bocavirus 1 [HBoV1]), Dependoparvovirus (e.g., adeno-associated virus 2 [AAV2]), Erythroparvovirus (e.g., parvovirus B19), Protoparvovirus (e.g., bufavirus 1 [BuV1]), and Tetraparvovirus (e.g., human parvovirus 4). No known human-infecting virus has been identified in the Amdoparvovirus, Artiparvovirus, Aveparvovirus, Copiparvovirus, or Loriparvovirus genera. The most recently identified emerging human pathogens of the Parvoviridae family belong to the Protoparvovirus [3,4,5]

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