Leisi, Remo; Di Tommaso, Chiarina; Kempf, Christoph; Ros, Carlos (2016). The Receptor-Binding Domain in the VP1u Region of Parvovirus B19. Viruses, 8(3), p. 61. Molecular Diversity Preservation International MDPI 10.3390/v8030061
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Parvovirus B19 (B19V) is known as the human pathogen causing the mild childhood disease erythema infectiosum. B19V shows an extraordinary narrow tissue tropism for erythroid progenitor cells in the bone marrow, which is determined by a highly restricted uptake. We have previously shown that the specific internalization is mediated by the interaction of the viral protein 1 unique region (VP1u) with a yet unknown cellular receptor. To locate the receptor-binding domain (RBD) within the VP1u, we analyzed the effect of truncations and mutations on the internalization capacity of the recombinant protein into UT7/Epo cells. Here we report that the N-terminal amino acids 5-80 of the VP1u are necessary and sufficient for cellular binding and internalization; thus, this N-terminal region represents the RBD required for B19V uptake. Using site-directed mutagenesis, we further identified a cluster of important amino acids playing a critical role in VP1u internalization. In silico predictions and experimental results suggest that the RBD is structured as a rigid fold of three α-helices. Finally, we found that dimerization of the VP1u leads to a considerably enhanced cellular binding and internalization. Taken together, we identified the RBD that mediates B19V uptake and mapped functional and structural motifs within this sequence. The findings reveal insights into the uptake process of B19V, which contribute to understand the pathogenesis of the infection and the neutralization of the virus by the immune system.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
UniBE Contributor: |
Leisi, Gian Remo, Kempf, Christoph (B), Ros Bascunana, Carlos |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry |
ISSN: |
1999-4915 |
Publisher: |
Molecular Diversity Preservation International MDPI |
Language: |
English |
Submitter: |
Christoph Kempf |
Date Deposited: |
19 Jan 2017 16:27 |
Last Modified: |
29 Mar 2023 23:35 |
Publisher DOI: |
10.3390/v8030061 |
BORIS DOI: |
10.7892/boris.91745 |
URI: |
https://boris.unibe.ch/id/eprint/91745 |
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