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

Bircher, Cornelia; Bieri, Jan; Assaraf, Ruben; Leisi, Remo; Ros, Carlos (2022). A Conserved Receptor-Binding Domain in the VP1u of Primate Erythroparvoviruses Determines the Marked Tropism for Erythroid Cells. Viruses, 14(2) 10.3390/v14020420

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)
08 Faculty of Science > Other Institutions > Teaching Staff, Faculty of Science

UniBE Contributor:

Bieri, Jan Lukas; Assaraf, Ruben Mordehai; Leisi, Gian Remo and Ros Bascunana, Carlos

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

1999-4915

Language:

English

Submitter:

Pubmed Import

Date Deposited:

01 Mar 2022 16:07

Last Modified:

01 Mar 2022 16:15

Publisher DOI:

10.3390/v14020420

PubMed ID:

35216013

Uncontrolled Keywords:

B19V VP1u VP1uR parvovirus B19 pig-tailed erythroparvovirus primate erythroparvovirus receptor rhesus erythroparvovirus simian erythroparvovirus tropism

BORIS DOI:

10.48350/166122

URI:

https://boris.unibe.ch/id/eprint/166122

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