Search our Database of Scientific Publications and Authors

I’m looking for a

    Details and Download Full Text PDF:
    The Receptor-Binding Domain in the VP1u Region of Parvovirus B19.

    Viruses 2016 Feb 24;8(3):61. Epub 2016 Feb 24.
    Department of Chemistry and Biochemistry, University of Bern, Bern 3012, Switzerland.
    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.
    PDF Download - Full Text Link
    ( Please be advised that this article is hosted on an external website not affiliated with
    Source Status
    Publisher SiteFound ListingPossible

    Similar Publications

    Parvovirus B19 uptake is a highly selective process controlled by VP1u, a novel determinant of viral tropism.
    J Virol 2013 Dec 25;87(24):13161-7. Epub 2013 Sep 25.
    Department of Chemistry and Biochemistry, University of Bern, Bern, Switzerland.
    The VP1 unique region (VP1u) of human parvovirus B19 (B19V) is the immunodominant part of the viral capsid. Originally inaccessible, the VP1u becomes exposed upon primary attachment to the globoside receptor. To study the function of the exposed VP1u in B19V uptake, we expressed this region as a recombinant protein. Read More
    The VP1u Receptor Restricts Parvovirus B19 Uptake to Permissive Erythroid Cells.
    Viruses 2016 Sep 28;8(10). Epub 2016 Sep 28.
    Department of Chemistry and Biochemistry, University of Bern, Bern 3012, Switzerland.
    Parvovirus B19 (B19V) is a small non-enveloped virus and known as the causative agent for the mild childhood disease. B19V has an extraordinary narrow tissue tropism, showing only productive infection in erythroid precursor cells in the bone marrow. We recently found that the viral protein 1 unique region (VP1u) contains an N-terminal receptor-binding domain (RBD), which mediates the uptake of the virus into cells of the erythroid lineage. Read More
    The globoside receptor triggers structural changes in the B19 virus capsid that facilitate virus internalization.
    J Virol 2010 Nov 8;84(22):11737-46. Epub 2010 Sep 8.
    Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.
    Globoside (Gb4Cer), Ku80 autoantigen, and α5β1 integrin have been identified as cell receptors/coreceptors for human parvovirus B19 (B19V), but their role and mechanism of interaction with the virus are largely unknown. In UT7/Epo cells, expression of Gb4Cer and CD49e (integrin alpha-5) was high, but expression of Ku80 was insignificant. B19V colocalized with Gb4Cer and, to a lesser extent, with CD49e. Read More
    The determinants for the enzyme activity of human parvovirus B19 phospholipase A2 (PLA2) and its influence on cultured cells.
    PLoS One 2013 15;8(4):e61440. Epub 2013 Apr 15.
    College of Life Sciences, Central China Normal University, Wuhan, China.
    Human parvovirus B19 (B19V) is the causative agent of erythema infectiosum in humans. B19 infection also causes severe disease manifestations, such as chronic anemia in immunocompromised patients, aplastic crisis in patients with a high turnover rate of red blood cells, and hydrops fetalis in pregnant women. Although a secreted phospholipase A2 (PLA2) motif has been identified in the unique region of the B19V minor capsid protein VP1(VP1u), the determinants for its enzyme activity and its influences on host cells are not well understood. Read More