A Conserved Receptor-Binding Domain in the VP1u of Primate Erythroparvoviruses Determines the Marked Tropism for Erythroid Cells.

Cornelia Bircher,Remo Leisi,Carlos Ros,Jan Bieri,Ruben Assaraf

doi:10.3390/v14020420

Cornelia Bircher, Remo Leisi + Show 3 more

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https://doi.org/10.3390/v14020420

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Journal: Viruses	Publication Date: Feb 17, 2022
Citations: 2	License type: CC BY 4.0

Affiliation: University of Bern, CSL (Switzerland)

Abstract

Parvovirus B19 (B19V) is a human pathogen with a marked tropism for erythroid progenitor cells (EPCs). The N-terminal of the VP1 unique region (VP1u) contains a receptor-binding domain (RBD), which mediates virus uptake through interaction with an as-yet-unknown receptor (VP1uR). Considering the central role of VP1uR in the virus tropism, we sought to investigate its expression profile in multiple cell types. To this end, we established a PP7 bacteriophage-VP1u bioconjugate, sharing the size and VP1u composition of native B19V capsids. The suitability of the PP7-VP1u construct as a specific and sensitive VP1uR expression marker was validated in competition assays with B19V and recombinant VP1u. VP1uR expression was exclusively detected in erythroid cells and cells reprogrammed towards the erythroid lineage. Sequence alignment and in silico protein structure prediction of the N-terminal of VP1u (N-VP1u) from B19V and other primate erythroparvoviruses (simian, rhesus, and pig-tailed) revealed a similar structure characterized by a fold of three or four α-helices. Functional studies with simian parvovirus confirmed the presence of a conserved RBD in the N-VP1u, mediating virus internalization into human erythroid cells. In summary, this study confirms the exclusive association of VP1uR expression with cells of the erythroid lineage. The presence of an analogous RBD in the VP1u from non-human primate erythroparvoviruses emphasizes their parallel evolutionary trait and zoonotic potential.

Highlights

Human parvovirus B19 (B19V), known as primate erythroparvovirus 1, is a small, nonenveloped icosahedral virus classified within the genus Erythroparvovirus of the familyParvoviridae [1]
PP7 was coupled to the heterobifunctional crosslinker trans-cyclooctene-PEG4 -NHS ester (TCO-NHS), and VP1 unique region (VP1u) was crosslinked to the heterobifunctional crosslinker MeTz-Mal
The receptor-binding domain (RBD) in the N-terminal of VP1u (N-VP1u) of B19V interacts with VP1uR for virus internalization into susceptible cells

Summary

Introduction

Human parvovirus B19 (B19V), known as primate erythroparvovirus 1, is a small, nonenveloped icosahedral virus classified within the genus Erythroparvovirus of the familyParvoviridae [1]. B19V infection causes an expanding range of syndromes, and factors influencing the severity of the infection are poorly understood. In individuals with underlying immune or hematologic disorders, B19V may cause severe cytopenias, myocarditis, vasculitis, glomerulonephritis, and encephalitis [3]. The infection has been frequently associated with arthropathies in adults and represents a risk factor for maternal–fetal transmission, causing fetal anemia, non-immune fetal hydrops, and fetal death [5,6]. B19V is transmitted primarily through the respiratory route by aerosol droplets [7]. The virus can be transmitted vertically to the developing fetus, via blood transfusion, contaminated plasma-derived therapeutic products, and organ transplantation [8–11]. Following the main entry through the respiratory route, the virus targets and productively exclusively infects erythroid precursor cells (EPCs) in bone marrow. The damage caused to the infected EPCs leads to the erythroid disorders during infection [12]

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